Pharmacokinetic and urine profile of tramadol and its major metabolites following oral immediate release capsules administration in dogs

The aim of the present paper was to test the oral administration of oral immediate release capsules of tramadol in dogs, to asses both its pharmacokinetic properties and its urine profile. After capsules administration of tramadol (4 mg/kg), involving eight male Beagle dogs, the concentration of tramadol and its main metabolites, M1, M2 and M5, were determined in plasma and urine using an HPLC method. The plasma concentrations of tramadol and metabolites were fitted on the basis of mono- and non-compartmental models, respectively. Tramadol was detected in plasma from 5 min up to 10 h in lesser amounts than M5 and M2, detected at similar concentrations, while M1 was detected in negligible amounts. In the urine, M5 and M1 showed the highest and smallest amount, respectively; M1 and M5 resulted widely conjugate with glucuronic acid. In conclusion, after oral administration of tramadol immediate release capsules, the absorption of the active ingredient was rapid, but its rapid metabolism quickly transformed the parental drug to high levels of M5 and M2, showing an extensive elimination via the kidney. Hence, in the dog, the oral immediate release pharmaceutical formulation of tramadol would have different pharmacokinetic behaviour than in humans.     

Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration

Tramadol, a centrally acting opioid analgesic with monamine reuptake inhibition, was administered to six alpacas (43-71 kg) randomly assigned to two treatment groups, using an open, single-dose, two-period, randomized cross-over design at a dose of 3.4-4.4 mg/kg intravenously (i.v.) and, after a washout period, 11 mg/kg orally. Serum samples were collected and stored at -80°C until assayed by HPLC. Pharmacokinetic parameters were calculated. The mean half-lives (t(1/2)) i.v. were 0.85±0.463 and 0.520±0.256 h orally. The Cp(0) i.v. was 2467±540 ng/mL, and the C(max) was 1202±1319 ng/mL orally. T(max) occurred at 0.111±0.068 h orally. The area under the curve (AUC(0-∞)) i.v. was 895±189 and 373±217 ng*h/mL orally. The volume of distribution (V(d[area])) i.v. was 5.50±2.66 L/kg. Total body clearance (Cl) i.v. was 4.62±1.09 h; Cl/F for oral administration was 39.5±23 L/h/kg. The i.v. mean residence time (MRT) was 0.720±0.264. Oral adsorption (F) was low (5.9-19.1%) at almost three times the i.v. dosage with a large inter-subject variation. This may be due to binding with the rumen contents or enzymatic destruction. Assuming linear nonsaturable pharmacokinetics and absorption processes, a dosage of 6.7 times orally would be needed to achieve the same i.v. serum concentration of tramadol. The t(1/2) of all three metabolites was longer than the parent drug; however, O-DMT, N-DMT, and Di-DMT metabolites were not detectable in all of the alpacas. Because of the poor bioavailability and adverse effects noted in this study, the oral administration of tramadol in alpacas cannot be recommended without further research.     

Terbinafine pharmacokinetics after single dose oral administration in the dog

Terbinafine is an allylamine antifungal prescribed for the treatment of mycoses in humans. It is increasingly being used in veterinary patients. The purpose of this study was to evaluate the pharmacokinetic properties of terbinafine in dogs after a single oral dose. Ten healthy adult dogs were included in the study. A single dose of terbinafine (30–35 mg/kg) was administered orally, and blood samples were periodically collected over a 24 h period during which dogs were monitored for adverse effects. Two of 10 dogs developed transient ocular changes. A high‐performance liquid chromatography assay was developed and used to determine plasma terbinafine concentrations. Pharmacokinetic analysis was performed using PK Solutions^® computer software. Area under the curve (AUC) from time 0 to 24 h was 15.4 μg·h/mL (range 5–27), maximal plasma concentration (C_max) was 3.5 μg/mL (range 3–4.9 μg/mL) and time to C_max (T_max) was 3.6 h (range 2–6 h). The time above minimal inhibitory concentration (T > MIC) as well as AUC/MIC was calculated for important invasive fungal pathogens and dermatophytes. The T > MIC was 17–18 h for Blastomyces dermatitidis, Histoplasma capsulatum and dermatophytes (Microsporum spp. and Trichophyton mentagrophytes), while the MIC for Sporothrix schenckii and Coccidioides immitis was exceeded for 9.5–11 h. The AUC/MIC values ranged from 9 to 13 μg h/mL for these fungi. Our results provide evidence supporting the use of terbinafine as an oral therapeutic agent for treating systemic and subcutaneous mycoses in dogs.     

Pharmacokinetic evaluation of oral dantrolene in the dog

The pharmacokinetics of dantrolene and its active metabolite, 5‐hydroxydantrolene, after a single oral dose of either 5 or 10 mg/kg of dantrolene was determined. The effects of exposure to dantrolene and 5‐hydroxydantrolene on activated whole‐blood gene expression of the cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) were also investigated. When dantrolene was administered at a 5 mg/kg dose, peak plasma concentration (C_max) was 0.43 μg/mL, terminal half‐life (t_1/2) was 1.26 h, and area under the time–concentration curve (AUC) was 3.87 μg·h/mL. For the 10 mg/kg dose, C_max was 0.65 μg/mL, t_1/2 was 1.21 h, and AUC was 5.94 μg·h/mL. For all calculated parameters, however, there were large standard deviations and wide ranges noted between and within individual dogs: t_1/2, for example, ranged from 0.43 to 6.93 h, C_max ratios ranged from 1.05 to 3.39, and relative bioavailability (rF) values ranged from 0.02 to 1.56. While activated whole‐blood expression of IL‐2 and IFN‐γ as measured by qRT‐PCR was markedly suppressed following exposure to very high concentrations (30 and 50 μg/mL, respectively) of both dantrolene and 5‐hydroxydantrolene, biologically and therapeutically relevant suppression of cytokine expression did not occur at the much lower drug concentrations achieved with oral dantrolene dosing.     

Pharmacokinetics of tramadol and its major metabolite after intramuscular administration in piglets

Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. Piglets might experience pain following castration, tooth clipping and tail docking and experimental procedures. The aim of this study was to assess the pharmacokinetics of T and its active metabolite M1 in male piglets after a single intramuscular injection. Six healthy male piglets were administered T (5 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals and drug plasma concentrations evaluated by a validated HPLC method. T plasma concentration was quantitatively detectable from 0.083 to 8 h. M1 was quantified over a shorter time period (0.083–6 h) with a T_max at 0.821 h. The study demonstrated that piglets produce a larger amount of M1 compared with dogs, horses and goats. The human minimum effective concentration of M1 (40 ng/mL) was exceeded for over 3 h in piglets. If it is assumed to also apply to piglets, it could be speculated that the drug efficacy might exert its action over 3 h or longer. This assumption has to be confirmed by further specific pharmacokinetic/pharmacodynamic studies.     

Pharmacokinetic study of enrofloxacin in Nile tilapia (Oreochromis niloticus) after a single oral administration in medicated feed

The objective of this study was to evaluate the disposition kinetics of enrofloxacin (ENR) in the plasma and its distribution in the muscle tissue of Nile tilapia (Oreochromis niloticus) after a single oral dose of 10 mg/kg body weight via medicated feed. The fish were kept at a temperature between 28 and 30 °C. The collection period was between 30 min and 120 h after administration of the drug. The samples were analyzed by high‐performance liquid chromatography with a fluorescence detector (HPLC‐FLD). The ENR was slowly absorbed and eliminated from the plasma (C_max = 1.24 ± 0.37 μg/mL; T_max = 8 h; T_1/2Ke = 19.36 h). ENR was efficiently distributed in the muscle tissue and reached maximum values (2.17 ± 0.74 μg/g) after 8 h. Its metabolite, ciprofloxacin (CIP), was detected and quantified in the plasma (0.004 ± 0.005 μg/mL) and muscle (0.01 ± 0.011 μg/g) for up to 48 h. After oral administration, the mean concentration of ENR in the plasma was well above the minimum inhibitory concentrations (MIC₅₀) for most bacteria already isolated from fish except for Streptococcus spp. This way the dose used in this study allowed for concentrations in the blood to treat the diseases of tilapia.     

Pharmacokinetics of mequindox and one of its major metabolites in chickens after intravenous, intramuscular and oral administration

Pharmacokinetics of mequindox and one of its major metabolites (M) was determined in chickens after intravenous (i.v.), intramuscular (i.m.) and oral administration of mequindox at a single dose of 10 (i.v. and i.m.) or 20 mg/kg b.w. (oral). Plasma concentration profiles were analyzed by a non-compartmental pharmacokinetic method. Following i.v., i.m. and oral administration, the areas under the plasma concentration-time curve (AUC(0-∞)) were 0.71±0.15, 0.67±0.21, 0.25±0.10 μg h/mL (mequindox) and 37.24±7.98, 36.40±9.16, 86.39±16.01 μg h/mL (M), respectively. The terminal elimination half-lives (t(1/2λz)) were determined to be 0.15±0.06, 0.21±0.09, 0.49±0.23 h (mequindox) and 5.36±0.86, 5.39±0.52, 5.22±0.35 h (M), respectively. The bioavailabilities (F) of mequindox were 89.4% and 16.6% for i.m. and oral administration. Steady-state distribution volume (V(ss)) of 1.20±0.34 L/kg and total body clearance (Cl(B)) of 13.57±2.16 L/kg h were determined for mequindox after i.v. dosing. After single i.m. and oral administration, peak plasma concentrations (C(max)) of 3.04±1.32, 0.36±0.13 μg/mL (mequindox) and 3.81±0.92, 5.99±1.16 μg/mL (M) were observed at t(max) of 0.08±0.02, 0.32±0.12 h (mequindox) and 0.66±0.19, 6.67±1.03 h (M), respectively. The results showed that mequindox was rapidly absorbed after i.m. or p.o. administration and most of mequindox was transformed to metabolites in chickens, with much higher C(max)s and AUCs of metabolite (M) than those of mequindox in plasma.     

Pharmacokinetics of mequindox and its metabolites in rats after intravenous and oral administration

Pharmacokinetics of mequindox (MEQ) and its metabolites were determined in rats after intravenous (i.v.) and oral (p.o.) administration of MEQ at a single dose of 10 mg kg⁻¹ bodyweight. After both administrations, MEQ and five of its metabolites were quantified, except M4, whereas M1 and M2 were the predominant ones. The areas under the concentration–time curves (h ng mL⁻¹) of MEQ, M1, M2, M3, M5 and M10 after i.v. administration were 7559 ± 495, 6354 ± 2761, 5586 ± 2337, 1034 ± 160, 2370 ± 791 and 1813 ± 622, respectively, whereas after p.o. administration, remained as 2809 ± 40, 4361 ± 3544, 4351 ± 1046, 1444 ± 814, 3864 ± 305 and 1213 ± 569, respectively. The elimination half-lives (h) of these compounds after i.v. administration were 3.48 ± 0.80, 4.20 ± 0.76, 6.25 ± 2.41, 4.77 ± 1.54, 4.69 ± 1.62 and 16.89 ± 5.15, respectively, and were 3.21 ± 0.40, 3.66 ± 1.06, 4.20 ± 1.03, 8.91 ± 5.99, 4.20 ± 2.02 and 20.84 ± 10.85 after p.o. administration, respectively. After p.o. administration, the bioavailability of MEQ was 37.16%. The results showed that MEQ was extensively metabolized in rats and rapidly absorbed after p.o. administration.     

Pharmacokinetics of mequindox and its metabolites in rats after intravenous and oral administration

Pharmacokinetics of mequindox (MEQ) and its metabolites were determined in rats after intravenous (i.v.) and oral (p.o.) administration of MEQ at a single dose of 10mgkg(-1) bodyweight. After both administrations, MEQ and five of its metabolites were quantified, except M4, whereas M1 and M2 were the predominant ones. The areas under the concentration-time curves (hngmL(-1)) of MEQ, M1, M2, M3, M5 and M10 after i.v. administration were 7559±495, 6354±2761, 5586±2337, 1034±160, 2370±791 and 1813±622, respectively, whereas after p.o. administration, remained as 2809±40, 4361±3544, 4351±1046, 1444±814, 3864±305 and 1213±569, respectively. The elimination half-lives (h) of these compounds after i.v. administration were 3.48±0.80, 4.20±0.76, 6.25±2.41, 4.77±1.54, 4.69±1.62 and 16.89±5.15, respectively, and were 3.21±0.40, 3.66±1.06, 4.20±1.03, 8.91±5.99, 4.20±2.02 and 20.84±10.85 after p.o. administration, respectively. After p.o. administration, the bioavailability of MEQ was 37.16%. The results showed that MEQ was extensively metabolized in rats and rapidly absorbed after p.o. administration.     

Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle

Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two-way cross-over design. Blood samples were taken serially over a 72-h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post-treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5-0.75 h up to 32 h post-administration, with a Cmax for the zwitterion suspension of 1.21 +/- 0.13 micrograms/ml and AUC of 18.55 +/- 1.45 micrograms.h/ml, respectively, which were significantly higher (P less than 0.01) than the Cmax (0.67 +/- 0.12 micrograms/ml) and AUC (8.57 +/- 0.91 micrograms.h/ml) for the trisamine solution. ABZSO2 was detected in plasma between 0.75 and 48 h post-administration. The zwitterion suspension resulted in a Cmax (2.91 +/- 0.10 micrograms/ml) and AUC (51.67 +/- 1.95 micrograms.h/ml) for ABZSO2, which were significantly higher (P less than 0.01) than those obtained for the trisamine solution (Cmax = 1.67 +/- 0.11 micrograms/ml and AUC = 22.77 +/- 1.09 micrograms.h/ml). The ratio of AUC for ABZSO2/ABZSO was 2.92 +/- 0.26 (zwitterion) and 2.80 +/- 0.20 (trisamine). The MRT for ABZSO2 was significantly longer (P less than 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of tramadol and o-desmethyltramadol in goats after intravenous and oral administration

The aim of this trial was to implement a method to obtain a tool for analyses of tramadol and the main metabolite, o-desmethyltramadol (M1), in goat's plasma, and to evaluate the pharmacokinetics of these substances following intravenous (i.v.) and oral (p.o.) administration in female goats. The pharmacokinetics of tramadol and M1 were examined following i.v. or p.o. tramadol administration to six female goats (2 mg/kg). Average retention time was 5.13 min for tramadol and 2.42 min for M1. The calculated parameters for half-life, volume of distribution and total body clearance were 0.94+/-0.34 h, 2.48+/-0.58 L/kg and 2.18+/-0.23 L/kg/h following 2 mg/kg tramadol HCl administered intravenously. The systemic availability was 36.9+/-9.1% and half-life 2.67+/-0.54 h following tramadol 2 mg/kg p.o. M1 had a half-life of 2.89+/-0.43 h following i.v. administration of tramadol. Following p.o., M1 was not detectable.     

Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration

Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations. Tramadol clearance, apparent volume of distribution at steady-state, mean residence time (MRT) and half-life after intravenous administration were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively. The MRT and half-life after intramuscular administration were 155+/-23 and 92+/-14 min. The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%. Tramadol was poorly absorbed after oral administration and only 3% of the administered dose was found in systemic circulation. The fate of the tramadol M1 metabolite was also investigated. M1 appeared to be a minor metabolite in horses, which could hardly be detected in plasma samples. The poor bioavailability after oral administration and the short half-life of tramadol may restrict its usefulness in clinical applications.     

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis)

Objective-To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Procedures-Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Results-Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Conclusions and Clinical Relevance-Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.     

Pharmacokinetics of mirtazapine and its main metabolites in Beagle dogs: a pilot study

Mirtazapine (MRT) is a human antidepressant drug mainly metabolised by the cytochrome P450 enzyme system to 8-OH mirtazapine (8-OH) and dimetilmirtazapine (DMR). The drug is usually administered to dogs with anorexia according to doses extrapolated from humans, although it could also have applications as an antidepressant and analgesic in this species. The aim of this study was to assess the pharmacokinetics of MRT and its metabolites, DMT and 8-OH. Six healthy male Beagle dogs were administered MRT orally (20 mg/dog) and plasma MRT and metabolite concentrations were evaluated by high performance liquid chromatography with fluorescence detection. The pharmacokinetic profiles of MRT and DMR were similar (detected from 0.25 up to 10 h), while 8-OH (detected from 0.50 up to 10 h) attained the highest concentrations. The mean half-life of MRT was 6.17 h with a clearance of 1193 mL/h/kg. The study showed that MRT has a different pharmacokinetic profile in the dog compared to other species.     

Evaluation of topical nalbuphine or oral tramadol as analgesics for corneal pain in dogs: a pilot study

Objective To evaluate the effectiveness of topical nalbuphine or oral tramadol in the treatment of corneal pain in dogs. Animals studied Fourteen male Beagle dogs. Procedures Dogs were divided into three treatment groups and sedated with dexmedetomidine (5 μ/kg IV). A 4 mm corneal epithelial wound was created in the right eye (OD) of all dogs. Sedation was reversed with atipamazole IM. All dogs received pre/post ophthalmic examinations. Post operatively, Group NB (n = 5) received topical 1% preservative‐free nalbuphine OD q8 h and an oral placebo PO q8 h. Group TR (n = 5) received tramadol (4 mg/kg) PO q8 h and topical sterile saline OD q8 h. Group CNTRL (n = 4) received topical sterile saline OD q8 h and an oral placebo q8 h. All dogs received topical 0.3% gentamicin OD TID until healed. Dogs were pain scored using a pain scoring system modified from the University of Melbourne pain scale at 0, 1, 2, 4, and 6 h, then every 6 h by observers masked to treatment, until corneal wounds were healed. Treatment failure was recorded if cumulative pain scores were above a minimum threshold of acceptable pain and rescue analgesia of morphine (1.0 mg/kg IM) was administered subsequently. Result Four dogs in Group NB, one dog in Group TR, and two dogs in Group CNTRL required rescue analgesia. There was no significant difference in the incidence of treatment failure between groups (P = 0.184). Mean time to rescue was 9.16 h. All corneal wounds were healed by 84 h. Conclusions The results of this study suggest tramadol rather than nalbuphine should be further investigated for the treatment of corneal pain.     

Pharmacokinetic studies of levofloxacin after oral administration in healthy and febrile cow calves

The present experiment was designed to study the pharmacokinetics of levofloxacin in six healthy cross bred female cow calves (4 to 6 months age) weighing between 40 to 80 kg. Plasma from blood was separated by centrifugation at 10,000 rpm. Quantitative estimation of levofloxacin was done by UV-VIS spectrophotometer at 286 nm. The mean maximum plasma concentration (Cp_max ) of levofloxacin in febrile calves (5.28?±?0.32 µg/ml) did not differ significantly as compared with healthy calves (4.50?±?0.22 µg/ml) after single dose (20 mg/kg) oral administration. The mean therapeutic plasma concentration ( Cp_ther ) of levofloxacin was maintained for longer period in febrile calves (10 h) as compared to healthy calves ( 8 h). The mean maximum urine concentration (Cu_max) in febrile (40.86?±?2.19 µg/ml) also did not differ significantly as compared with healthy calves (39.38?±?2.43 µg/ml). No significant difference in various pharmacokinetic parameters of plasma was observed in healthy calves ( β?=?0.23?±?0.01/h ; t1/2 β?=?3.00?±?0.17 h and MRT?=?4.66?±?0.14 h ) and febrile calves ( β?=?0.23?±?0.01/ h; t1/2 β?=?3.05?±?0.16 h and MRT?=?5.04?±?0.14 h ) . The mean value of β, and t ½ β calculated in urine also did not differ between healthy and febrile calves. However, the value of MRT(3.79?±?0.07 h) and Cl_B(1.65?±?0.09 ml/kg/min) calculated in urine of febrile calves significantly(p?B?=?2.09?±?0.13 ml/kg/min). Based on kinetic profile levofloxacin may be given orally at the dose rate of 1.49 mg/kg B.W.at 8 h intervals in febrile calves.     

Pharmacokinetic profiles of meloxicam after single IV and PO administration in Bilgorajska geese

The purpose of this study was two-fold: I) to determine the pharmacokinetic profile of meloxicam (MLX) in geese after intravenous (IV) and oral (PO) administration and II) to assess tissue residues in muscle, heart, liver, lung, and kidney. Ten clinically normal female Bilgorajska geese were divided into two groups (treated, n = 8; control, n = 2). Group 1 underwent a 3-phase parallel study with a 1-week washout period. In phase I, animals received MLX (0.5 mg/kg) by IV administration; the blood was collected up to 48 hr. In phases II and III geese were treated orally at the same dosage for the collection of blood and tissue samples, respectively. Group 2 served as control. After the extraction procedure, a validated HPLC method with UV detection was used for plasma and organ analysis. The plasma concentrations were quantifiable up to 24 hr after both the administrations. The elimination phase of MLX from plasma was similar in both the administration groups. The clearance was slow (0.00975 L/hr*Kg), the volume of distribution small (0.0487 L/kg), and the IV half-life was 5.06 ± 2.32 hr. The average absolute PO bioavailability was 64.2 ± 24.0%. Residues of MLX were lower than the LOQ (0.1 µg/kg) in any tested tissue and at any collection time. The dosage used in this study achieved the plasma concentration, which provides analgesia in Hispaniolan Amazon parrots for 5 out of 24 hr after PO administration. MLX tissue concentrations were below the LOD of the assay in tissue (0.03 µg/ml). A more sensitive technique might be necessary to determine likely residue concentrations in tissue.     

Pharmacokinetic evaluation of a slow-release cefotaxime suspension in the dog and in sheep

Three Merino ewes were given cefotaxime IM, and 3 were given cefotaxime subcutaneously (50 mg/kg of body weight each); each dose was suspended in 6 ml of oil. Five dogs were also given an oily suspension of cefotaxime subcutaneously (SC) (50 mg/kg of body weight). The plasma concentrations (Cp) and pharmacokinetic data obtained after cefotaxime in the oily suspension was injected IM and SC were compared with data from the same animals after they were given an aqueous solution of cefotaxime by the same routes. Key pharmacokinetic values obtained after cefotaxime was administered IV to sheep and to dogs are discussed. Mean peak Cp (Cpeak) in sheep when given the oily suspension IM was approximately 53 micrograms/ml at 0.18 to 0.40 hour, and that value in sheep given the aqueous preparation was 62 micrograms/ml 0.08 to 0.18 hour. Mean Cpeak values after the oily suspension and the aqueous preparation were injected SC were 11.0 micrograms/ml (between 0.8 and 1 hour) and 51 micrograms/ml (between 0.25 and 1 hour), respectively. Bioavailabilities were approximately 70% after IM injection was done and 90% after SC injection was done. The beta-plasma half-lives were 0.7 hour after IM injection was done and 2.9 hours after SC injection was done. Mean Cpeak in dogs when given the oily suspension SC was 30 micrograms/ml at 1.0 hour, and when dogs were given the aqueous preparation SC, Cpeak was 27 micrograms/ml at 0.6 hour. Absorption was virtually complete after the oily suspension and aqueous preparations were given.(ABSTRACT TRUNCATED AT 250 WORDS)