Selection of an aminoglycoside antibiotic for administration to horses

The serum concentrations of the aminoglycosides neomycin, kanamycin and streptomycin were determined after intravenous (iv) and intramuscular (im) administration. These values were then related to the minimum inhibitory concentrations (MIC) of a number of equine pathogenic bacteria to determine the duration of therapeutic serum concentrations of the aminoglycosides in the horse. Pharmacokinetic analysis of the data using neomycin as the example revealed a mean (+/- sd) peak serum concentration of 23.2 +/- 10.2 micrograms/ml present at 30 mins, and at 8 h the serum concentration was 2.8 +/- 0.8 micrograms/ml. From the pharmacological analysis of concentration-time data it was shown that neomycin was very rapidly absorbed from the im injection site, with an absorption half-time of 0.16 +/- 0.05 and was well absorbed (systemic availability was 73.7 +/- 26.9 per cent). A peak tissue level, which represented 40 per cent of the amount of drug in the body, was obtained at 32 mins after injection of the drug. At 8 h, the fractions of the dose in the central and peripheral compartments of the model were 1.5 per cent and 2.5 per cent respectively, and 96 per cent was the cumulative amount eliminated up to that time. Based on the MIC values of the majority of isolates of Corynebacterium equi, and only a few isolates of Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Streptococcus equi, one would expect a serum concentration of more than 2 micrograms neomycin/ml up to 8 h following im dosage (10 mg/kg) to be therapeutically effective.     

Pharmacokinetics of ceftazidime in sheep and its penetration into tissue and peritoneal fluids

Serum, tissue and peritoneal fluid concentrations of ceftazidime were studied in ewes after intravenous, intramuscular and subcutaneous administration at 50 mg kg-1 bodyweight. Tissue and peritoneal cages were implanted in the animals studied. After intravenous bolus administration, the mean serum concentration versus time profile was best described by a two-compartment open model. The distribution rate constant (alpha) was 3.5 +/- 1.1 h-1 and the half-life (t 1/2 alpha) 0.22 +/- 0.09 hour. The elimination rate constant (beta) was 0.43 +/- 0.04 h-1 and half-life (t 1/2 beta) 1.6 +/- 0.2 hours. The area under the curve was 275.7 +/- 84.0 micrograms.ml-1 h. The volume of distribution as steady state was 356.1 +/- 208.0 ml kg-1. The penetration ratio into tissue fluid was 62.6 +/- 15.1 per cent and into peritoneal fluid 61.1 +/- 16.5 per cent. After intramuscular injection, the elimination half-life was 1.7 +/- 0.2 hours, the area under the curve was 228.7 +/- 43.3 micrograms.ml-1 h. and the elimination rate constant was 0.42 +/- 0.05 h-1. The penetration ratio into tissue fluid was 68.5 +/- 37.3 per cent and into peritoneal fluid 73.3 +/- 34.4 per cent. After subcutaneous injection, the elimination half-life was 1.8 +/- 0.5 hours, the area under the curve was 231.8 +/- 65.6 micrograms.ml-1 h. and the elimination constant was 0.41 +/- 0.10 h-1. The penetration ratio into tissue fluid was 47.2 +/- 3.5 per cent and into peritoneal fluid 58.1 +/- 15.6 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of miocamycin following intravenous administration to cattle

The plasma pharmacokinetics for a single intravenous dose (10 mg/kg body weight) of miocamycin (a 16-membered macrolide drug) was investigated in Holando Argentino cattle (n = 5). Blood drug concentrations were determined by a microbiological method and data were best-fitted to a two-compartment open model. The pharmacokinetic profile consisted of a short distribution phase (t1/2 alpha = 7.41 +/- 0.53 min), followed by an extended terminal elimination phase (t1/2 beta = 2.49 +/- 0.23 h). The volume of distribution at steady-state was large (2.13 +/- 0.17 l/kg), suggesting extensive tissue distribution, the clearance value was 0.60 +/- 0.03 l/h.     

Pharmacokinetics of tylosin in broiler chickens

Biological availability and pharmacokinetic properties of tylosin were determined in broiler chickens after oral (p.o.) and intravenous (i.v.) administration at a dose of 10 mg/kg. The calculated bioavailability--F%, by comparing AUC values--p.o. and AUC--i.v., ranged from 30%-34%. After intravenous injection tylosin was rapidly distributed in the organism, showing elimination half-life (t1/2 beta) values of 0.52 h and distribution volume (Vd) of 0.69 L/kg, at a clearance rate (Cl) of 5.30 +/- 0.59 ml/min/kg. After oral administration, tylosin has a similar distribution volume (Vd = 0.85 L/kg), while the elimination half-life t1/2 beta of 2.07 h was four times bigger than after i.v. administration at Cl = 4.40 +/- 0.27 ml/min/kg. The obtained value tmax = 1.5 h for tylosin after oral administration indicates that using this antibiotic with drinking water in broiler chickens is the method of choice. However, a relatively low value Cmax = 1.2 micrograms/ml after oral administration of tylosin shows that dosing of this antibiotic in broiler chickens should be higher than in other food producing animals.     

Disposition kinetics of tylosin administered intravenously and intramuscularly in desert sheep and Nubian goats

The pharmacokinetic behaviour of tylosin was compared in five Desert sheep and five Nubian goats. The animals were given a single dose of 20% tylosin (15 mg/kg), either intravenously (i.v.) or intramuscularly (i.m.). Following i.v. administration, the volumes of distribution and the elimination half-life times were similar in both species, whereas in goats a greater volume of the central compartment and faster clearance were observed. For the i.m. route, similar pharmacokinetics were observed in both species. The bioavailability (f) of the drug in goats (0.84 +/- 0.11) was not significantly higher than that in sheep (0.73 +/- 0.08). The present study has shown that, despite the significant differences in some of the drug pharmacokinetic parameters between sheep and goats for the i.v. route, identical intravenous and intramuscular dosage regimens of tylosin may be recommended for the two species.     

Disposition kinetics and dosage regimen of ceftriaxone in crossbred calves (short communication).

Disposition kinetics and urinary excretion of ceftriaxone were investigated in healthy crossbred calves after its single intravenous administration (10 mg kg-1). Based on kinetic parameters, an appropriate dosage regimen of ceftriaxone in calves was calculated. The peak plasma level of ceftriaxone at 1 min was 84.0 +/- 1.55 micrograms ml-1 which declined to 0.43 +/- 0.05 microgram ml-1 at 8 h. The value of elimination half-life (t1/2 beta), volume of distribution Vd (area) and total body clearance (ClB) were 4.39 +/- 0.63 h, 1.91 +/- 0.19 L kg-1 and 0.31 +/- 0.01 L kg-1 h-1, respectively. Approximately 41 per cent of total administered drug was recovered in the urine within 24 h of its administration. The plasma protein binding of ceftriaxone was found to be concentration dependent with an overall mean of 38.55 per cent. The binding capacity of ceftriaxone to plasma proteins and the dissociation rate constant of protein-drug complex were 20.1 x 10(-8) +/- 18.4 x 10(-8) mole g-1 and 1.07 x 10(-6) +/- 0.52 x 10(-6) mole, respectively. An appropriate intravenous dosage regimen of ceftriaxone in cattle would be 12 mg kg-1 repeated at 24 h.     

Pharmacokinetic study of neomycin in calves following intravenous and intramuscular administration.

Neomycin sulfate was administered to calves by the intravenous and intramuscular routes. Serum drug levels were determined and the intravenous pharmacokinetic parameters derived using the Gauss-Newton nonlinear fitting algorithm and the two compartment open model. The kinetic parameters determined were as follows: zero time intercept, serum drug level 68.045 +/- 15.894 micrograms/mL, alpha slope intercept 37.666 +/- 13.874 micrograms/mL and beta slope intercept 30.379 +/- 12.638 micrograms/mL; equilibration rate (pool I and II) 0.081 +/- 9.064 min-1; elimination rate 0.004 +/- 0.001 min-1; half-time alpha 14.774 +/- 11.236 min, half-time beta 166.596 +/- 47.576 min; first order elimination constant 0.009 +/- 0.002 min+; transfer rate constants, central to peripheral, 0.032 +/- 0.026 min+ and peripheral to central 0.045 +/- 0.037 min-1; volume of central compartment 0.186 +/- 0.047 L/kg; volume of distribution 0.388 +/- 0.130 L/kg; body clearance 0.002 +/- 0.001 L/kg/min.     

Disposition Kinetics,Bioavailability and Renal Clearance of Cefepime in Calves

The pharmacokinetics of cefepime were studied following intravenous and intramuscular administration of 6.5 mg/kg in four female Friesian calves. Following single intravenous administration, the serum concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2)beta) was 2.38+/-0.16 h, volume of distribution at steady state (Vdss) was 0.21 +/- 0.01 L/kg, and total body clearance (ClB) was 1.1 +/- 0.08 ml/min per kg. Following intramuscular administration, the drug was rapidly absorbed with an absorption half-life (t(1/2)ab) of 0.29+/-0.02 h; maximum serum concentration (Cmax) of 21.7 +/- 1.1 microg/ml was attained after (Tmax) 1.1 +/- 0.08 h; and the drug was eliminated with an elimination half-life (t(1/2)el) of 3.02 +/- 0.18 h. The systemic bioavailability (F) after intramuscular administration of cefepime in calves was 95.7% +/- 7.44%. The in vitro serum protein-binding tendency was 10.5-16.7%. Following administration by both routes, the drug was excreted in high concentrations in urine for 24 h post administration.     

Pharmacokinetics of cefepime administered by i.v. and i.m. routes to ewes

The pharmacokinetics of cefepime were studied following i.v. and i.m. administration of 20 mg/kg in 10 ewes. Following i.v. administration of a single dose, the plasma concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2beta)) was 1.76 +/- 0.07 h, volume of distribution at steady-state [V(d(ss))] was 0.32 +/- 0.01 L/kg and total body clearance (Cl(B)) was 2.37 +/- 0.05 mL/min.kg. Following i.m. administration, the drug was rapidly absorbed with an absorption half-life (t(1/2ab)) of 0.49 +/- 0.05 h, maximum plasma concentration (Cmax) of 31.9 +/- 1.5 mug/mL was attained at (tmax) 1.1 +/- 0.2 h and the drug was eliminated with an elimination half-life (t(1/2el)) of 2.06 +/- 0.11 h. The systemic bioavailability (F) after i.m. administration of cefepime was 86.8 +/- 7.5%. The extent of plasma protein binding measured in vitro was 14.8 +/- 0.54%. The drug was detected in urine for 36 h postadministration by both routes.     

Disposition of tylosin in goats

The disposition kinetics of tylosin was studied in goats after intravenous (i.v.) or intramuscular (i.m.) injection of 15 mg/kg body wt. Following i.v. injection, tylosin was rapidly and widely distributed with a distribution half-life of 0.2 h and volume of distribution of 1.7 l/kg. It was slowly eliminated with a mean elimination half-life of 3.04 h and a total body clearance rate of 6.8 ml/kg/min. Following i.m. injection, tylosin was slowly absorbed (tau 1/2 ab of 1.82 h). Tylosin concentration in serum was greater than 1 microgram/ml after 1 h and persisted up to 12 h post-injection. The peak concentration (Cmax 2.38 micrograms/ml) was obtained after 4.19 h. The systemic bioavailability of tylosin injected intramuscularly was 72.6% and the serum protein bound fraction was 37.59% of the total drug. Tylosin was excreted in milk and urine at concentrations much higher than that in serum. Low concentrations of tylosin were reported in ruminal juice of goats. In conclusion tylosin should be injected every 14 h to obtain an appreciable concentration in serum, milk and urine.     

Pharmacokinetics and dosage of chlorpromazine in goats

Pharmacokinetic parameters which describe the distribution and elimination of chlorpromazine in goats were determined. Following the intravenous administration of a single dose (2.5 mg/kg), disposition of the drug was described in terms of the biexponential expression C _p= Ae^-αt+ Be^-βt. Based on total (free and bound) chlorpromazine levels in plasma, pseudo-distribution equilibrium was rapidly attained, and the elimination half-life was 1.51 ± 0.48 h (mean ± SD, n = 8). Total body clearance, which is the sum of all clearance processes, was 80 ± 25 ml/min/kg. The curves of an animal representative of the group, based on individual rate constants associated with the two-compartment open model, showed that at 5 h after drug administration 8% and 6% of the dose were present in the peripheral and central compartments, respectively. The kinetic parameters of chlorpromazine determined at a dosage level of 10 mg/kg body weight in six goats showed that the drug followed first-order kinetics and kinetic parameters were similar after both dose levels. Based on these findings and therapeutic plasma levels, a satisfactory intravenous regimen should be 2.0 – 3.5 mg/kg and the drug action will persist for 5–6 h.     

Effect of short term starvation on disposition kinetics of chloramphenicol in goats

The effect of short term starvation on the disposition kinetics of chloramphenicol was determined in goats. The same dosage level (10 mg kg-1) administered intravenously produced higher serum concentrations in the animals when they were starved than when they were not starved. This could be attributed to the significantly smaller (P less than 0.05) volume of the central compartment. Starvation significantly decreased the rate of elimination of chloramphenicol while the apparent volume of distribution of the drug was not altered. A significant decrease in the body clearance, 1.36 +/- 0.95 ml (min kg)-1 in the starved condition compared with 3.78 +/- 2.19 mg (min kg)-1 in the controls, caused a corresponding increase in the half life of chloramphenicol. The decreased rate of elimination was attributed to decreased hepatic microsomal metabolism since starvation did not change the fraction of the dose excreted unchanged in the urine. The clinical significance of the altered disposition of chloramphenicol is that administration at the usual dosing rate would lead to accumulation of the drug and eventual toxicity.     

Pharmacokinetics and pharmacodynamics of piroxicam in dogs

Piroxicam was administered to beagle dogs intravenously and orally at a dose rate of 0.3 mg/kg bodyweight. It had an elimination half-life of 40.2 hours, a volume of distribution of 0.29 +/- 0.02 litres/kg and a body clearance rate of 0.066 litres/hour. When administered orally it was 100 per cent bioavailable and maximum plasma concentrations were achieved quickly (3.1 +/- 1.0 hours). Piroxicam inhibited the generation of thromboxane B2 in the blood of dogs by more than 70 per cent and more than 50 per cent inhibition was maintained in most animals for 48 hours.     

Pharmacokinetics of intravenous and oral methimazole following single-and multiple-dose administration in normal cats

The pharmacokinetics of methimazole (MMI) administered intravenously and orally were determined in six adult domestic shorthaired cats. There was no significant difference between mean serum MMI concentrations after oral and i.v. administration by 30 min post-MMI administration, indicating relatively rapid and complete absorption of the drug. The bioavailability of MMI ranged from 27% to 100% (mean = 81.1 +/- 11.4%). The mean serum elimination half-life was 6.6 +/- 2.0 h, with a wide range of values (1.9 h to 15.1 h). After repeat i.v. administration of MMI following 2 weeks of oral administration of the drug, no significant difference was found between mean serum concentrations after single-dose and multiple-dose administration. No significant change in serum elimination half-life or total body clearance was found after multiple-dose administration of MMI. Two cats with the longest half-lives (9.9 h and 15.1 h), however, did exhibit markedly shorter t1/2 values (3.5 h and 3.3 h, respectively) after multiple-dose administration. Values for central and steady state volumes of distribution also decreased after multiple-dose administration, possibly indicating saturation of thyroid uptake of MMI with chronic administration. These results indicate that MMI has good oral bioavailability and has a longer mean serum elimination half-life than propylthiouracil, the other anti-thyroid drug that has been evaluated in cats. Although no significant change in mean values occurred after multiple-dose administration of MMI, drug-induced acceleration of metabolism may occur in some cats after long-term MMI administration.     

Pharmacokinetics of phenobarbital in the cat following intravenous and oral administration.

Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat.     

Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal

Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12.8 +/- 2.1 h. The mean (+/- se) volume of distribution was 0.86 +/- 0.026 litres/kg bwt and mean (+/- se) total body clearance was 0.0564 +/- 0.0065 litres/kg bwt/h. Sedation was noticed 15 to 20 mins after the beginning of infusion and lasted for up to 8 h. All foals could be aroused and could walk although they were ataxic for the first 1 to 2 h. A degree of delayed hyperexcitability occurred 3 to 8 h after infusion. In equine neonatal seizure disorders it is recommended to use a loading dose of 20 mg/kg bwt of phenobarbital, followed by maintenance doses of 9 mg/kg bwt at 8 h. With this regimen, average steady state serum phenobarbital concentrations should range between approximately 11.6 and 53 micrograms/ml. Phenobarbital serum concentrations should be monitored following the loading dose and 24 h after initiating the maintenance doses to check that levels remain within the suggested (human) therapeutic range of 15 to 40 micrograms/ml.     

Pharmacokinetics and tissue residues of pefloxacin and its metabolite norfloxacin in broiler chickens

1. The pharmacokinetics of pefloxacin and its active metabolite norfloxacin were investigated in chickens after a single oral administration of pefloxacin at a dosage of 10 mg/kg. To characterise the residue pattern, another group of chickens was given 10 mg of pefloxacin/kg body once daily for 4 d by oral route; the tissue concentrations of pefloxacin and norfloxacin were determined at 1, 5 and 10 d after the last administration of the drug. 2. The concentrations of pefloxacin and norfloxacin in plasma and tissues were determined by HPLC assay. The limit of detection for pefloxacin and norfloxacin was 0.03 microg/ml in plasma or microg/g in tissue. 3. The plasma concentration-time data for pefloxacin and norfloxacin were characteristic of a one-compartment open model. The elimination half-life, maximum plasma drug concentration, time to reach maximum plasma drug concentration and mean residence time of pefloxacin were 8.74 +/- 1.48 h, 3.78 +/- 0.23 microg/ml, 3.33 +/- 0.21 h and 14.32 +/- 1.94 h, respectively, whereas the respective values of these variables for norfloxacin were 5.66 +/- 0.81 h, 0.80 +/- 0.07 microg/ml, 3.67 +/- 0.21 h and 14.44 +/- 0.97 h. 4. Pefloxacin was metabolised to norfloxacin to the extent of 22%. 5. The concentrations of pefloxacin (microg/g) 24 h after the fourth dose of the drug declined in the following order: liver (3.20 +/- 0.40) > muscle (1.42 +/- 0.18) > kidney (0.69 +/- 0.04) > skin and fat (0.06 +/- 0.02). Norfloxacin was also detectable in all the tissues analysed except muscle. No drug and/or its metabolite was detectable in tissues except skin and fat 5 d after the last administration. The concentrations of pefloxacin and norfloxacin in skin and fat 10 d after the last dose of pefloxacin were 0.04 +/- 0.02 and 0.03 +/- 0.01 microg/g, respectively.     

Disposition of tylosin in goats.

The disposition kinetics of tylosin was studied in goats after intravenous or intramuscular injection of 15 mg/kg b. wt. Following i.v. injection, tylosin was rapidly and widely distributed in goats (half life of distribution: 0.2 h and volume of distribution: 1.7 l/kg). It was slowly eliminated with a mean elimination half life of 3.04 h and a total body clearance rate of 6.8 ml/kg/min. Following i.m. injection, tylosin was slowly absorbed (T1/2ab of 1.82 h). Tylosin concentration in serum was greater than 1 microgram/ml after 1 h and persisted up to 12 h post-injection. The peak concentration (Cmax, 2.38 micrograms/ml) was obtained after 4.19 h. The systemic bioavailability of tylosin injected intramuscularly was 72.6% and the serum protein bound fraction was 37.6% of the total drug. Tylosin was excreted in milk and urine at concentrations much higher than that in serum. Low concentrations of tylosin were reported in ruminal juice of goats. In conclusion tylosin should be injected every 15 hours to obtain an appreciable concentration in serum, milk and urine.     

Pharmacokinetics and tissue residue profiles of erythromycin in broiler chickens after different routes of administration

This study investigated the disposition kinetics and plasma availability of erythromycin in broiler chickens after single intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.) and oral administrations (p.o.) of 30 mg kg(-1) b. wt. Tissue residue profiles were also studied after multiple intramuscular, subcutaneous, and oral administration of 30 mg kg(-1) b. wt., twice daily for three consecutive days. Plasma and tissue concentrations of erythromycin were determined using microbiological assay methods with Micrococcus luteus as the test organism. Following intravenous injection, plasma concentration-vs-time curves were best described by a two compartment open model. The decline in plasma drug concentration was bi-exponential with half-lives of (t(1/2alpha)) 0.19 h and (t(1/2beta)) 5.3 h for distribution and elimination phases, respectively. After intramuscular, subcutaneous and oral administration erythromycin at the same dose was detected in plasma at 10 min and reached its minimum level 8 h post-administration. The peak plasma concentration (Cmax) were 5.0, 5.3, and 6.9 microg x ml(-1) and were attained at 1.7, 1.4, and 1.3 h (Tmax), respectively. The elimination half-lives (T(1/2el)) were 3.9, 2.6, and 4.1 h and the mean residence times (MRT) were 3.5, 3.2, and 3.6 h, respectively. The systemic bioavailabilities were 92.5, 68.8, and 109.3%, respectively. In vitro protein binding percent of erythromycin in broiler plasma was ranged from 21 to 31%. The limit of quantification (LOQ) for the assay was 0.03 microg x ml(-1) in plasma and tissues. The tissue level concentrations were highest in the liver, and decreased in the following order: plasma > kidney > lung > muscle and heart. No erythromycin residues were detected in tissues and plasma after 24 h except in liver and kidney where it persisted during 48 h following intramuscular and oral administrations.     

The bioavailability, dispostion kinetics and dosage of sulphadimethoxine in dogs.

The disposition kinetics of sulphadimethoxine were studied in six normal beagle dogs after intravenous injection of a single dose (55 mg/kg). The median (range) distribution and elimination half times of the drug were 2.36 (2.06-3.35) hours and 13.10 (9.71-16.50) hours, respectively. Total body clearance of the drug had a median value of 21.7 ml/kg/h and a mean value of 21.4 ml/kg/h. While the overall tissue to plasma level ratio (k12/k21) of the drug was 0.55 after distribution equilibrium had been attained, analogue computer simulated curves showed that at 24 hours the fractions (percentage) of the dose in the central and tissue compartments were 12 and 11%, respectively. The drug was shown, by equilibrium dialysis method, to be highly bound to plasma proteins (greater than 75%) within the usual therapeutic range (50 to 150 mug/ml) of plasma levels. The systemic availability of sulphadimethoxine from the oral suspension was 32.8% (22.5-80.0). Since the absorption half time, 1.87 (0.86-3.22) hours, was considerably shorter than the half-life, 13.10 (9.71-16.50) hours, of the drug, the rate of absorption would have little influence on the dosage regimen. Based on the experimental data obtained, a satisfactory dosage regimen might consist of a priming dose of 55 mg/kg by the intravenous route and maintenance doses of either 27.5 mg/kg of sulphadimethoxine injection given intravenously or 55 mg/kg of the oral suspension administered at 24 hour intervals. The adequacy and duration of therapy will depend upon the clinical response obtained.