Pharmacokinetics of gentamicin in mares in late pregnancy and early lactation

The disposition of drugs may differ between pregnant and nonpregnant animals, necessitating a change in dosage. We hypothesized that volume of distribution or clearance may be different for aminoglycoside antibiotics in pregnant mares vs. nonpregnant lactating mares. To examine this hypothesis, we administered gentamicin sulfate to seven Thoroughbred and Quarterhorse mares on two occasions, followed by plasma drug gentamicin assay and pharmacokinetic analysis. The first dose was administered 1-4 weeks before parturition (mean weight 578 kg) and the second dose was administered in the period 1-4 weeks after parturition (mean weight 518 kg). The dose administered at each time was approximately 6.6 mg/kg, intravenously (i.v.). Plasma gentamicin concentrations were determined using fluorescence polarization immunoassay and pharmacokinetic analysis was performed using a two-compartment open model. The plasma concentration vs. time profiles and total area-under-the-curve were almost identical for mares at late gestation vs. early lactation. Mean volume of distribution at steady-state was 0.15 (+/-0.02) and 0.16 (+/-0.03) L/kg, systemic clearance was 1.06 (+/-0.17) and 1.11 (+/-0.17) mL/kg/min, and mean (harmonic) elimination half-life was 2.2 and 2.1 h, for pregnant and nonpregnant mares, respectively. We concluded that there were no differences in drug distribution and clearance between pregnant and nonpregnant lactating mares. Gentamicin was also assayed in plasma of newborn foals after an injection of 6.6 mg/kg to three of the mares within 60 min of parturition. Gentamicin was undetectable in plasma samples from these foals and, therefore, apparently does not cross the placenta of mares at term.     

Comparative effects and safety of ivermectin in pregnant mares

Mares (n=20) approaching 3 months of pregnancy were assigned randomly to 1 of 4 treatment groups. Treatments were (a) an IM injection of ivermectin at 600 mcg/kg, (b) various conventional anthelmintic drugs at the manufacturers' recommended dose, (c) and IM injection of the ivermectin vehicle (placebo) and (d) no anthelmintic treatment during the trial. All anthelmintic treatments were administered at 60-day intervals up to and including the date of parturition. Fecal egg counts, arginase, hemoglobin and packed cell volume values were determined at bi-weekly intervals during the trial and there were no statistically significant differences determined between the treatment groups for these parameters. None of the mares showed any adverse clinical signs during the course of this study and all 20 mares delivered live foals which remained on the research farm until they were sold as year-lings. Mares treated with ivermectin had significantly (P<0.01) lower egg per gram counts than mares in the conventional treatment group. Multiple hematological and clinical chemistry values were determined for all mares and resulting foals within 12 hours post-parturition. A one-way analysis of variance showed no clinically relevant statistically significant differences between treatment groups in either mares or foals at 12 hours post-parturition. This study suggests that ivermectin at 600 mcg/kg is safe and highly efficacious when administered to pregnant mares.     

Efficacy of ivermectin in controlling Strongyloides westeri infections in foals

Twenty-eight foals whose dams were treated IM with ivermectin (200 micrograms/kg of body weight) on the day of parturition were compared with 35 foals whose dams were administered only the vehicle. The effect of ivermectin on the vertical transmission of Strongyloides westeri and foal heat diarrhea was determined by a comparison of results obtained in the 2 groups. Foals from treated mares had significantly fewer S westeri eggs per gram of feces from 17 to 28 days postpartum. There were no differences observed in the frequencies of severity of foal heat diarrhea between the treated and control groups. In another experiment, using the same foals, 32 foals were treated IM with ivermectin (200 micrograms/kg) at 21 days of age and were compared with 31 foals administered only the vehicle. Significantly fewer S westeri eggs were recovered from the ivermectin-treated foals on day 26 to day 32, the completion day of the trial.     

Control of cyathostome infections in mares treated at parturition with ivermectin

Six mares were treated on the day of parturition with an intramuscular injection of 0.2 mg kg-1 ivermectin and placed in a pasture free of equine parasites as soon as possible after foaling. The mares and their foals were compared with a similar group of untreated mares and foals on an adjoining pasture. The experimental data was derived from mare and foal fecal egg counts, foal necropsies and pasture larval counts. Ivermectin administered to mares on the day of parturition, when combined with movement to parasite-free pastures, significantly lowered the cyathostome (small strongyle) egg production for 4 months. This reduced cyathostome exposure was reflected in lower worm-burdens in their foals for 5 months. The results indicate that ivermectin will effectively control equine strongyles when mares and their foals are moved to parasite-free pastures.     

Efficacy of ivermectin in the treatment of induced Parascaris equorum infection in pony foals

Eighteen pony foals inoculated with 1,500 +/- 109 infective Parascaris equorum eggs were given 0.02 ml of ivermectin vehicle (liquid)/kg of body weight, PO, (control); 0.2 mg of ivermectin paste/kg, PO; or 0.2 mg ivermectin liquid/kg, PO, on postinoculation day (PID) 28. Foals were euthanatized on PID 42, and the small intestinal contents were examined for P equorum larvae. The mean number of fourth-stage P equorum larvae in foals treated with ivermectin paste and liquid were 3.5 and 6, respectively. Significantly (P less than 0.01) higher mean numbers of larvae (1,250) were detected in foals treated with ivermectin vehicle. Larvae recovered from foals treated with ivermectin vehicle were of significantly (P less than 0.002) longer mean length than those from foals treated with ivermectin paste or liquid. Gross examination of lungs and liver revealed similar pathologic changes from the migration of P equorum in all foals. Adverse reaction to treatment was not observed.     

Evidence of Ivermectin Resistance by Parascaris equorum on a Texas Horse Farm

By collecting fecal samples every 2 weeks beginning at 2 months of age, 32 foals from a single Texas farm were monitored. The foals were administered ivermectin paste at the time of the first collection and again monthly. When foals had Parascaris egg counts higher 2 weeks after ivermectin treatment than at treatment, they were administered pyrantel pamoate at the manufacturer's recommended dose (6.6 mg/kg) or at twice the recommended dose (13.2 mg/ kg) when tapeworm eggs were also detected. An elevation or only minimal reduction (less than 75%) in Parascaris egg counts was seen 2 weeks after ivermectin treatment until the foals were 8 months of age, at which time there was an 85% reduction in fecal egg count after treatment. When pyrantel was administered at the manufacturer's recommended dose, a 42% to 84% reduction in egg counts occurred, but at 13.2 mg/kg there was a 98% to 100% reduction in fecal egg counts 2 weeks posttreatment. However, pyrantel failed to control strongylate egg counts even at the elevated dose, whereas ivermectin reduced strongylate fecal egg counts by greater than 99%, determined 2 weeks posttreatment. Pyrantel, but not ivermectin, lowered Parascaris egg counts. Ivermectin, but not pyrantel, lowered strongyle egg counts 2 weeks post administration. A single drug for all ages of horses approach to parasite control requires rethinking. Combinations of drugs or more careful evaluation of anthelmintics in foals may be necessary for continued parasite control.     

The safety of ivermectin administered orally to pregnant mares

The effect of ivermectin on the first 3 months of equine fetal development was investigated by postnatal evaluation of ontogeny; one trial was conducted in New Jersey, USA and another was conducted simultaneously in Dammartin-en-Serve, France. A total of 58 mares were used including 32 horse-mares (USA) and 26 Welsh-type pony mares (France). An oral dose of 600 micrograms ivermectin per kilogram of body weight (therapeutic dose x 3) was given to each treated mare as a paste formulation during the first 2 weeks following refusal of breeding service and at 2-week intervals thereafter for a total of 6 doses during fetal organogenesis. Control groups were given drug-free paste vehicle at 12 weekly intervals or were not dosed. Teratogenic anatomical defects were not discernible in the progeny of either medicated or unmedicated mares. Production of weaned healthy yearlings was used as a measure of reproductive efficiency. Such yearlings were produced by 65.5% of the pregnant mares that received no ivermectin. In contrast, a higher reproductive efficiency of 75.8% occurred in pregnant mares that received six timed elevated doses of ivermectin during the first 13 weeks of fetal development. Ivermectin did not adversely affect the fertility of mares or the organogenesis of their developing foals.     

Pharmacokinetics of gentamicin in newborn to 30-day-old foals

Gentamicin sulfate, equivalent to 4 mg of gentamicin base/kg of body weight, was administered IV to 6 Thoroughbred foals on day 1 (12 to 24 hours of age) and at 5, 10, 15, and 30 days after birth. On day 40 after parturition, gentamicin was given to the mares at a dosage similar to that used in foals. Decay of serum gentamicin concentrations was best described by a 2-compartment model. Among foals, the overall elimination rate constant at 30 days of age was significantly (P less than 0.05) greater than at days 1, 10, and 15. There was, however, no difference in the overall elimination rate constant between foals and mares. The volume of distribution (Vd), determined on the basis of total area under the disposition curve, did not change between day 1 and day 30. Mean values of Vd of foals were between 1.5 and 2.5 times higher than the mean Vd of the mares; however, only values from the foals at days 5 and 10 were significantly greater. Both age and interindividual differences were reflected in the total body clearance (ClB) of gentamicin. Total body clearance of gentamicin of foals on day 1 was less than that of foals on days 5, 10, and 30. Additionally, C1B of gentamicin on day 15 was less than that on day 30. There was no significant difference between ClB of foals and mares except for the day-30 group, which had a higher clearance rate than did the adults. Protein binding of gentamicin was less than 30% in all groups, and there were no apparent age-related differences.     

Field efficacy of ivermectin plus praziquantel oral paste against naturally acquired gastrointestinal nematodes and cestodes of horses in North America and Europe

The efficacy of an oral formulation of ivermectin plus praziquantel in the reduction of nematode and cestode egg counts in horses was assessed in 273 horses under field conditions at 15 sites in North America (n = 6) and Europe (n = 9). Horses were confirmed by fecal examination to have natural infections of strongyles (100%) and tapeworms (76%). Replicates of four horses were formed at each site, and in each replicate three animals received ivermectin (0.2 mg/kg body weight) plus praziquantel (1 mg/kg body weight) oral paste and one animal remained untreated or received vehicle paste. Fecal samples were collected for fecal nematode and cestode egg counting before and 7, 8, 9, 14, 15, and 16 days after treatment. Horses treated with ivermectin plus praziquantel oral paste had significantly (P <.01) lower posttreatment strongylid and cestode egg counts (reductions of 98% or more) than controls. Combined site analyses revealed that 95% or 96% of the horses positive for cestode eggs before treatment that were treated with ivermectin plus praziquantel were negative for cestode eggs at each posttreatment fecal examination. No adverse reactions attributable to ivermectin plus praziquantel oral paste treatments were observed. The results of the studies demonstrated that ivermectin plus praziquantel paste was highly effective in reducing egg shedding by gastrointestinal nematodes and cestodes, and no adverse reactions were observed in horses treated under field conditions.     

Use of febantel or ivermectin for treatment of calves with experimentally induced Bunostomum phlebotomum infection

In the first of 2 separate trials, the efficacy of febantel, given at a dosage of 5 mg/kg of body weight, was assessed in calves with 60-day experimentally induced Bunostomum phlebotomum infection. Ten calves were given febantel paste, and 10 were given the vehicle only. All 20 calves were necropsied 7 days after cessation of treatment. Compared with untreated calves, febantel-treated calves harbored 99.4% fewer nematodes. In the second trial, the efficacy of ivermectin, given as a paste formulation at a dosage of 0.2 mg/kg, was assessed in calves with experimentally induced B phlebotomum infection. Ivermectin was given at 18 (n = 6) and 60 (n = 6) days after infection. At each treatment date, 3 additional calves were given vehicle only. At 67 days after infection, all calves were euthanatized. Efficacies of ivermectin against 18- and 60-day infections were 100 and 99.8%, respectively. Both anthelmintic preparations were easily administered, and adverse reactions were not observed.     

The effect of nonspecific immunostimulation of pregnant mares with 1,3/1,6 glucan and levamisole on the immunoglobulins levels in colostrum, selected indices of nonspecific cellular and humoral immunity in foals in neonatal and postnatal period

The objectives of the studies were to evaluate the effect of levamisole and 1,3/1,6 glucan applied in pregnant mares on parameters of non-specific cellular and humoral immunity of foals. Eighteen mares in three experimental groups (six animals in each) and their progeny were examined. Multiparous mares, crossbreed of Polish, full-blood and Hannover lines (400-500 kg), 4-9 years old, originated from four different farms. They were kept under identical zoohygienic and nutritional conditions. The animals were randomly chosen in experimental groups. None of mares had been previously vaccinated. In group I, levamisole was injected three times at 7-day intervals at a dose of 2.5 mg/kg of body weight. Group II was injected at the same periods of time and manner with 1,3/1,6 glucan at a dose of 0.19 mg/kg of body weight, whereas mares in group III served as controls. Injection of the immunostimulators started in mares 4-6 weeks before expected parturition. Blood was taken from foals before the first dose of colostrum, then 18 and 36 h after the first dose of colostrum and on Days 7, 14, 21, 28, 35, 42, 49 and 56 of life. The parameters determined in blood were reduction of NBT by PMNs, phagocytic activity, phagocytic index, test of intracellular killing and in blood sera were total protein, gamma-globulin fraction, lysozyme activity, level of IgG, IgG(T), IgM and IgA. In the first dose of colostrum taken just after parturition, specific gravity, total protein, gamma-globulin complex, lysozyme activity, level of IgG, IgG(T), IgM, IgA were determined. Colostrum of mares immunostimulated with levamisole or 1,3/1,6 glucan were characterized by a high content of IgG and IgG(T) compared to the colostrum of nonstimulated mares. The level of immunity was higher in foals from dams immunostimulated with levamisole or 1,3/1,6 glucan. Clinical examinations in neonatal and postnatal period did not show any abnormalities in these foals.     

Effects of vitamin E and selenium administration on pregnant,heavy draft mares on placental retention time and reproductive performance and on white muscle disease in their foals

This study investigated the effects of administering vitamin E and selenium to pregnant heavy draft horsemares on the incidence of retained placenta and postpartum reproductive performance and on the prevention of the white muscle disease in their foals. In study A, 1,000 mg of vitamin E and 50 mg of selenium (E-SE 20 mL) were given to 22 mares 3 weeks before expected parturition (335 days counted from last mating), whereas 28 mares were used as controls. In study B, E-SE were administered 2 weeks before expected parturition at 2 dose levels, with 25 mares receiving 20 mL E-SE, 19 mares receiving 10 mL, and 29 mares kept as controls. Vitamin E and selenium were assayed in serum collected from some of the mares before administration of E-SE and again postpartum and from the foals immediately after birth. Serum selenium concentrations before E-SE administration were deficient (<65 ng/mL) in all mares (n = 48) but were increased in the postpartum sample from treated mares regardless of the dose or timing of administration (n = 31) (P = .05). Only study B mares were deficient in vitamin E prepartum, and both dose levels of E-SE had corrected this in the postpartum sample (P = .01). All foals were selenium deficient regardless of whether their dams had received E-SE or not, although concentrations were higher in foals from treated study A mares than from controls (P = .05). Mares with the highest selenium concentrations prepartum (40 ng/mL and over) had shorter placental retention times than mares with lower selenium concentrations (P = .05) and did not respond to E-SE with a further reduction in retention time. By contrast, mares with prepartum selenium concentrations between 20 and 40 ng/mL tended to respond to E-SE with a shortened placental retention time (P = .07). E-SE administration reduced the mean number of days from parturition to last mating (nonpregnant term) in study B mares (P = .05) and in mares with adequate prepartum vitamin E concentrations (>300 g/mL, P = .05). We conclude that maintaining high level serum vitamin E and selenium concentrations of prepartum mares is expected to increase fertility of selenium-deficient mares. Therefore, the regimen of vitamin E and selenium administrations to selenium deficient mares should be developed.     

Anthelmhntic effects of injectable and oral paste formulations of ivermectin against 28-day infections of parascaris equorum

Efficacy of ivermectin treatment (0.2 mg/kg) against 28-day experimental infections of Parascaris equorum was determined in 18 pony foals6–17.5 weeks old. There were 6 foals in each group: nontreated control, ivermectin injectable or oral paste. In comparison with larvae found in the nontreated controls, ivermectin injectable or paste was 96.0% and 99.9% efficacious. There was a distinct difference in drug effect against the larger (ca 26mm.) vs the smaller (13–19mm) larvae by the 2 formulations of ivermectin. There were no adverse signs related to treatment of the young foals.     

Comparison of the efficacy of ivermectin, oxibendazole, and pyrantel pamoate against 28-day Parascaris equorum larvae in the intestine of pony foals

Sixteen helminth-free pony foals were inoculated with a mean (+/- SD) 2,000 (+/- 545.5) infective Parascaris equorum eggs (day 0). Foals were allocated to replicates of 4, and treatments within each replicate were assigned at random. Treatment administered on postinoculation day (PID) 28 included no treatment (control), 0.2 mg of ivermectin/kg of body weight, 10 mg of oxibendazole/kg, or 6.6 mg of pyrantel base (pamoate)/kg. Paste formulations of the anthelmintics were administered orally. The foals were euthanatized 14 days after treatment (PID 42) and examined for P equorum larvae in the small intestine. The mean +/- SD (and range) numbers of fourth-stage P equorum larvae recovered from nontreated foals and those treated with ivermectin, pyrantel, or oxibendazole were 1,603.8 +/- 1,026.8 (305 to 2,480), 29.3 +/- 55.8 (0 to 113), 413.0 +/- 568.1 (0 to 1,204), or 889.5 +/- 1,123.1 (1 to 2,345), respectively. Compared with the value for control (nontreated) foals, treatment with ivermectin, pyrantel, and oxibendazole was 98.2, 74.2, and 44.5% effective, respectively, when administered 28 days after experimentally induced infection with P equorum. Adverse reactions attributable to treatment were not observed.     

Field safety evaluation of cambendazole in horses

Cambendazole paste 31% w/w, at 20 and 40 mg/kg, was tested in a series of field trials involving 237 horses of various ages, sex and pregnancy status. No drug-related sequelae were observed except for a mild anorexia in 10 thoroughbreds in training and on concentrate feed. Forty-nine thoroughbred mares, more than three months pregnant, showed no drug-related sequelae to themselves or their foals. Of 10 dosed at 80 or 160 mg/kg, one (80 mg/kg) showed elevated temperature at % hours after dosing.

Faecal egg counts were reduced 99% when conducted on 86 cambendazole treated animals seven to eight days after dosing at 20 or 40 mg/kg.     

Safety of altrenogest in pregnant mares and on health and development of offspring

Fifty-one light-horse mares were utilized to evaluate the safety of an oral progestin, altrenogest, administered throughout gestation on: gestation length, embryonic and fetal loss, periparturient events, health and development of offspring, and future reproductive capabilities of the mares. Pregnancies were established by inseminating mares with 250 × 10⁶ progressively motile spermatozoa from the same stallion every other day throughout estrus or by non-surgical transfer of embryos. Mares were randomly assigned to 1 of 2 treatments upon confirmation of pregnancy on day 20: 1) controls, 2 ml of neobee oil orally per 44.5 kg of body weight; and 2) treated, 2 ml of altrenogest dissolved in neobee oil at a concentration of 2.2 mg/ml orally per 44.5 kg of body weight. Treatments were administered daily from day 20 to 320 of gestation.There were no significant differences between treatment groups for duration of gestation, placental weight, time to placental expulsion and incidence of retained placental membranes. Number of female foals born from altrenogest treated mares (14 of 23) was greater (P<.05) than the number from untreated control mares (4 of 16). Female foals born from altrenogest treated mares had larger clitori (P<.05) than those from control mares. Times to sternal recumbency, standing and nursing were similar for the 2 groups (P>.05). Body weight and height at withers, heart girth circumference and length and width of cannon were measured at time of birth and at 2, 4, 6, 8, 12 and 16 weeks of age. Measurements did not differ (P>05) between treated and control foals for any development parameters.Beginning on day 20 postpartum, mares were teased daily. During estrus, mares were inseminated every other day with 250 × 10⁶ motile spermatozoa. Teasing and/or insemination was continued for 2 cycles or until mares were 35 days pregnant. The number of mares pregnant after 1 cycle and after 2 cycles of insemination was similar (P>.05) for treated and control mares. Nineteen of 21 treated mares and 15 of 16 control mares were pregnant after 2 cycles of insemination. Number of cycles per pregnancy was similar (P>.05) for treated and control mares (1.37 vs 1.13) as was number of days mares exhibited estrus (6.30 vs 6.13). Number of inseminations per cycle did not differ (P>.05) between treated and control mares (2.92 vs 3.00). In summary, there was no effect of treatment with altrenogest from day 20 to 320 of gestation on periparturient events, viability and growth of offspring and subsequent reproductive performance of mares.     

Effect of omeprazole paste on intragastric pH in clinically normal neonatal foals

OBJECTIVE: To evaluate the efficacy of omeprazole paste, a commonly used antiulcer drug, on intragastric pH in clinically normal neonatal foals. ANIMALS: 6 clinically normal foals between 5 and 14 days of age. PROCEDURE: Intragastric pH was recorded in each foal by use of a disposable antimony pH electrode with internal reference. Values for intragastric pH were recorded every 4 seconds by use of an ambulatory pH monitor. There were two 24-hour recordings of intragastric pH for each foal, with 24 hours between recordings. Foals were not administered any drugs during the first recording. Foals were administered omeprazole paste (4 mg/kg, PO) 1 hour after the start of the second recording. Mean pH was calculated for each hour of each 24-hour recording session. Hourly mean values were compared between the first and second 24-hour recordings. RESULTS: Complete data were obtained from 4 of 6 foals during the first 24-hour recording and 6 of 6 foals during the second 24-hour recording. Foals had significantly higher mean hourly intragastric pH for hours 2 to 22 following omeprazole administration, compared with corresponding hourly pH values in foals during the first recording. CONCLUSION AND CLINICAL RELEVANCE: Omeprazole paste can effectively increase intragastric pH in clinically normal neonatal foals within 2 hours after oral administration of the first dose and can be administered to neonatal foals at the rate of 4 mg/kg, PO, every 24 hours.     

Passive transfer failure in horses: incidence and causative factors on a breeding farm

A prospective study was performed to determine the incidence and associated maternal and managemental factors of failure of passive transfer (FPT) in foals on a breeding farm. The zinc sulfate turbidity test (ZSTT) and latex agglutination test (LAT) were compared for accuracy in estimating serum immunoglobulin (Ig)G of foals, as determined by single radial immunodiffusion (SRID). Complete past and present foaling histories of 136 Standardbred mares were obtained. All foalings were witnessed by farm attendants, and colostral samples were collected from mares within 2 hours after parturition. Foals that did not rise and nurse were supplemented with colostrum from the dam, using a bottle or nasogastric tube. Serum samples were prepared from foals and mares between 24 and 36 hours after parturition, and from some mares 45 to 90 days before parturition. Serum IgG concentrations of mares and foals and colostral whey were determined, using SRID. Serum IgG also was estimated in foals, using ZSTT and a commercially available LAT. Four of the 136 foals (2.9%) had FPT (serum IgG less than or equal to 400 mg/dl). Serum IgG concentrations in foals significantly correlated with colostral IgG (P less than 0.001). A significantly larger proportion of foals with FPT were bottle-fed their colostrum (P less than 0.01). Month of parturition, mare age, parity, number of barren seasons, incidence of assisted births or retained placenta, or prepartum serum IgG concentrations did not significantly affect colostral IgG concentrations or serum IgG concentrations in foals. As serum IgG concentrations in foals decreased and as colostral IgG concentrations decreased, the proportion of mares that prelactated significantly (P less than 0.01) increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of detomidine (Domosedan) on the maintenance of equine pregnancy and foetal development: ten cases

Detomidine was administered throughout 10 pregnancies in eight mares. An intravenous injection of 20 micrograms/kg body weight was given weekly from Day 14 to Day 60 of gestation and thereafter every four weeks until parturition. One mare suffered torsion of the large colon and was destroyed on Day 86; the foetus was normally developed. A further mare aborted at 167 days. The remaining eight pregnancies continued to full term. One foal was delivered by caesarean section because of torticollis and, of the seven foals born spontaneously, one had bilateral upward patellar fixation at one month old. Therefore, although only six of the 10 foals developed normally, the other four cases showed no pathological similarities to suggest a common cause. Although these data were based on a small number of mares, they did not suggest that the repeated administration of detomidine had specific adverse effects on the pregnancies.     

Changes in liver copper concentration of thoroughbred foals from birth to 160 days of age and the effect of prenatal copper supplementation of their dams

OBJECTIVES: To monitor the change in liver copper concentration of Thoroughbred foals from birth to 160 days of age and to determine the effects of supplementation by two injections of copper edetate given to dams in late gestation on the liver copper concentration of their foals at birth. PROCEDURE: Ten mares pregnant to the same stallion were randomised into two groups on the basis of age, liver copper concentration and expected foaling date. The treatment group mares were given 100 mg and 250 mg copper edetate intramuscularly during the ninth and tenth months of gestation respectively. Foals had liver biopsies taken weekly in the first month of life, then monthly for four months. Foals were euthanased at 160 days of age; liver samples were taken and the copper concentrations were determined. RESULTS: Two distinct patterns of age dependent decline in liver copper concentration were evident. The mean (+/- SD) liver copper concentration of the foals was high at birth (374 +/- 130 mg/kg DM), and for seven it declined to adult values by 160 days of age (21 +/- 6 mg/kg DM). In three foals the decline was at a slower rate than in the other seven and at 160 days of age the mean concentration was 162 +/- 32 mg/kg DM. Repeated measures analysis showed significant differences between each biopsy (P < 0.01) and between 'normal' and 'accumulator' foals (P < 0.002). Copper injections given to mares in late pregnancy had no effect on the liver copper concentration of foals at birth. CONCLUSIONS: The significance of the two patterns of age dependant decline in liver copper concentration is unknown. Parenteral copper supplementation of the dam in late gestation had no effect on the liver copper concentration of the foal at birth.