Interspecies differences in the pharmacokinetics of kanamycin and apramycin

Comparative studies on some selected pharmacokinetic parameters for kanamycin in sheep, goats, rabbits, chickens and pigeons, and for apramycin in sheep, rabbits, chickens and pigeons were carried out after intravenous administration of the two drugs at a dose of 10 mg/kg. The results revealed that a two-compartment open model was most suitable for kanamycin, while for apramycin a one-compartment open model was usually optimal. The log distribution rate constant (alpha) of kanamycin was significantly correlated to the log of the body mass (r = 0.919, n = 5, p < 0.05). Interspecies differences in the apparent volume of distribution (Vda) of kanamycin were small. These differences were larger for apramycin, as were the variations in the area under the serum concentration-time curve (AUC) and in the total body clearance (ClB) of both kanamycin and apramycin, both having almost a threefold difference depending on the species but without any correlation to body mass. The values of the log half-life of kanamycin in the mammals in this study and also those from data in the literature revealed a significant correlation with log body mass between animal species according to the equation: t1/2 beta = 38.47W0.21 (r = 0.7648, n = 10, p < 0.05).     

Clinical pharmacokinetics of amikacin in dogs

After IV, IM, and subcutaneous injection of single dosages of amikacin (5, 10, and 20 mg/kg of body weight) in each of 4 dogs, the elimination kinetics of amikacin were determined. The pattern of urinary excretion and cumulative amount excreted unchanged in 24 hours were also determined. Amikacin had a short half-life (approx 1 hour) that was independent of the dosage. Intravenous injection of 10 mg/kg gave apparent volume of distribution of 226 +/- 37 ml/kg and body clearance of 2.64 +/- 0.24 ml/min.kg (mean +/- SD, n = 4). Within 6 hours, greater than 90% of the antibiotic was excreted in the urine, regardless of the route of administration. For isolates of common bacterial species from the canine urinary tract, minimum inhibitory concentrations of amikacin, gentamicin, tobramycin, and kanamycin were determined in vitro. Cumulative percentages were approximately the same for urinary isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and coagulase-positive staphylococci that were susceptible (minimum inhibitory concentrations less than or equal to 32 micrograms/ml) to increasing concentrations of amikacin, gentamicin, and tobramycin, in vitro. Klebsiella pneumoniae was significantly more susceptible to amikacin than were the other bacteria evaluated. Widest variations in susceptibility to aminoglycosides were found with urinary isolates of streptococcal species. For dogs with normal renal function, an amikacin dosage of 10 mg/kg (IM or subcutaneously) is recommended every 8 hours for treatment of systemic infections, and every 12 hours for treatment of urinary tract infections caused by susceptible bacteria.     

Allometric scaling of marbofloxacin, moxifloxacin, danofloxacin and difloxacin pharmacokinetics: a retrospective analysis

The purpose of this study was to examine the allometric analyses of marbofloxacin, moxifloxacin, danofloxacin and difloxacin using pharmacokinetic data from the literature. The parameters of interest (half-life, clearance and volume of distribution) were correlated across species as a function of body weight using an allometric approach (Y = aWb). Results of the allometric analysis indicated similarity between clearance and volume of distribution as they relate to body weight for all drugs. The elimination half-life was independent of body mass for all fluoroquinolones except moxifloxacin. Results of the analysis suggest that allometric scaling can be used as a tool for predicting pharmacokinetic parameters for fluoroquinolones.     

Comparative pharmacokinetics of enrofloxacin in mice, rats, rabbits, sheep, and cows.

OBJECTIVE: To compare pharmacokinetic variables of enrofloxacin (ENR) after IV administration in mice, rats, rabbits, sheep, and cows and to perform allometric analysis of ENR. ANIMALS: 47 mice, 5 rats, 5 rabbits, 5 sheep, and 5 cows. PROCEDURE: Serially obtained plasma samples were assayed for ENR concentration, using high-performance liquid chromatography. In vitro plasma protein binding was determined by ultrafiltration. Plasma ENR concentration versus time curves were fitted by use of nonlinear least-squared regression analysis. Pharmacokinetic variables were correlated further with body weight. RESULTS: In all species studied, the best fit was obtained for a two-compartment open model; ENR half-life ranged from 89 minutes in mice to 169 minutes in cows. Volume of distribution was large in all species studied, with values ranging from 10.5 L/kg in mice to 1.5 L/kg in sheep. Body clearance ranged from 68.1 ml/min/kg for mice to 4.6 ml/min/kg for sheep. Unbound ENR was found to be (mean +/- SD) 58+/-2, 50+/-6, 50+/-2, 31+/-2, and 40+/-3% in plasma of mice, rats, rabbits, sheep, and cows, respectively. The only pharmacokinetic variables that could be correlated with body weight were elimination half-life, clearance, and volume of distribution. Allometric exponents denoting proportionality of half-life, body clearance, and volume of distribution with body weight were 0.06, 0.82, and 0.90, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: An allometric approach could provide a suitable method for determining a scale for ENR pharmacokinetics among various mammalian species. This would faciliatate the administration of appropriate doses of ENR to all animals.     

Allometric analysis of ciprofloxacin and enrofloxacin pharmacokinetics across species

The purpose of this study was to examine the allometric analysis of ciprofloxacin and enrofloxacin using pharmacokinetic data from the literature. The pharmacokinetic parameters used were half-life, clearance and volume of distribution. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula Y = aW(b), where Y is half-life, clearance or volume of distribution, W the body weight and a is an allometric coefficient (intercept) that is constant for a given drug. The exponential term b is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. A total of 21 different species of animals were studied. Results of the allometric analyses indicated similarity between clearance and volume of distribution as they related to body weight for both drugs. Results of the current analyses indicate it is possible to use allometry to predict pharmacokinetic variables of enrofloxacin or ciprofloxacin based on body size of species. This could provide information on appropriate doses of ciprofloxacin and enrofloxacin for all species.     

Interspecies allometric analysis of the comparative pharmacokinetics of 44 drugs across veterinary and laboratory animal species

The purpose of this study was to apply the method of allometric analysis to a study of the comparative disposition of veterinary drugs using the Food Animal Residue Avoidance Databank (FARAD) as a source of the comparative pharmacokinetic data. An initial filtration of the FARAD data was performed in order to exclude drugs for which no pharmacokinetic data were available, in at least four species the route of administration was other than intravenous, and the matrix was different from blood, plasma or serum. This process restricted the study to a total of 44 candidate drugs. The primary pharmacokinetic parameter selected for study was half-life (t_1/2). As this parameter is a composite of clearance (Cl) and volume of distribution (Vd), it was considered to be the most robust for interspecies scaling. Volume of distribution at steady state (Vd_ss) and clearance showed weak allometric correlations with weight across species. The relationships between body weight and elimination half-life (t_1/2β) were determined for this selected group of drugs by using the empirically determined function Y=a W^b. The function Y represents the parameter of concern (half-life), a is a coefficient typical of every drug (intercept), W is the species average body weight, and b is the scaling exponent. A total of 11 drugs (tetracycline, oxytetracycline, chlortetracycline, erythromycin, diazepam, prednisolone, cephapirin, ampicillin, gentamicin, apramycin and carbenicillin) showed statistically significant correlations and consequently are excellent candidates for interspecies extrapolation of pharmacokinetic parameters (half-life) in species of relevance to veterinary medicine. The remaining 33 drugs were divided into two groups which showed various degrees of lack of correlation. Many of the drugs that showed no allometric correlation were low hepatic extraction drugs. However, some other drugs demonstrated equivocal results which could either be due to a true lack of allometric correlation, or be inconclusive due to the lack of quality data or excessive variability due to the multi-laboratory origin of the FARAD data. The results of this study show that interspecies scaling is applicable to certain veterinary drugs. The experimental determination of the coefficients of the allometric equation for relevant pharmacokinetic parameters (clearance and volume of distribution) could be an important tool in estimating dose in species where the drug has never been studied. This could have important consequences in terms of avoiding the use of dose-titration studies in Phase I of drug development, for drugs that are experimentally ‘well behaved’.     

Allometric analysis of thiamphenicol disposition among seven mammalian species

The pharmacokinetics of thiamphenicol (TAP), a broad-spectrum antibiotic, was determined in male mice, rats, rabbits, dogs, pigs, sheep and calves. The relationship between the main pharmacokinetic parameters of TAP and body weight (W) was studied across these seven mammalian species, using double-logarithmic plots. The experimental values of volume of distribution (Vss), clearance (Cl) and elimination half-life (t(1/2)beta) were plotted, and extrapolated values were determined from corresponding allometric equations. These parameters were fitted to the following equations: Vss=0.98W0.92, Cl=15.80W0.76 and t(1/2)beta=0.94W0.20, and present good correlation (Vss: r2=0.997, P < 0.001; Cl: r2=0.976, P < 0.001, t(1/2)beta: r2=0.852, P < 0.005), that is expected of a drug eliminated primarily by renal glomerular filtration, with insignificant hepatic metabolism. For the t(1/2)beta, the extrapolated and observed values were similar. The extrapolated values of Cl were close to the experimental values, except for the mouse and pig mean percent error [(M.E.) equal to 62 and 119%, respectively], while the extrapolated and observed values for the Vss were very similar. The comparison between experimental and extrapolated values suggests that it could be possible to extrapolate, with good prediction, the kinetic parameters of this drug for mammalian species, using allometric scaling, except for the species that eliminate the drug by a combination of renal excretion and hepatic metabolism.     

Comparison of amikacin pharmacokinetics in a killer whale (Orcinus orca) and a beluga whale (Delphinapterus leucas).

Amikacin, an aminoglycoside antimicrobial, was administered to a killer whale (Orcinus orca) and a beluga whale (Delphinapterus leucas) for the treatment of clinical signs consistent with gram-negative aerobic bacterial infections. Dosage regimens were designed to target a maximal plasma concentration 8-10 times the minimum inhibitory concentrations of the pathogen and to reduce the risk of aminoglycoside toxicity. Allometric analysis of published pharmacokinetic parameters in mature animals yielded a relationship for amikacin's volume of distribution, in milliliters, given by the equation Vd = 151.058(BW)1.043. An initial dose for amikacin was estimated by calculating the volume of distribution and targeted maximal concentration. With this information, dosage regimens for i.m. administration were designed for a killer whale and a beluga whale. Therapeutic drug monitoring was performed on each whale to assess the individual pharmacokinetic parameters. The elimination half-life (5.99 hr), volume of distribution per bioavailability (319 ml/kg). and clearance per bioavailability (0.61 ml/min/kg) were calculated for the killer whale. The elimination half-life (5.03 hr), volume of distribution per bioavailability (229 ml/kg). and clearance per bioavailability (0.53 ml/min/kg) were calculated for the beluga whale. The volume of distribution predicted from the allometric equation for both whales was similar to the calculated pharmacokinetic parameter. Both whales exhibited a prolonged elimination half-life and decreased clearance when compared with other animal species despite normal renal parameters on biochemistry panels. Allometric principles and therapeutic drug monitoring were used to accurately determine the doses in these cases and to avoid toxicity.     

Effects of halothane anesthesia on the clearance of gentamicin sulfate in horses

Inhalation anesthetics decrease the clearance of some drugs that are eliminated by renal excretion. The purpose of the study reported here was to investigate the effects of halothane anesthesia on the pharmacokinetics and urinary excretion of gentamicin sulfate, using the horse as a model. Using a crossover design, pharmacokinetic values after a single IV dose of gentamicin (4 mg/kg) were compared in halothane-anesthetized and unanesthetized horses. Compared with unanesthetized horses, the anesthetized horses had significant decreases in total body clearance (P less than 0.01) and apparent volume of distribution (P less than 0.05), and a significant increase in half-life (P less than 0.05) of gentamicin.     

Pharmacokinetics of tobramycin in ducks and sex-related differences

The aims of the present study were to determine the disposition of tobramycin after single intravenous (IV) and intramuscular (IM) injections in ducks, and to establish any sex-related differences. Tobramycin sulfate was administered as a 2.5% water solution in a cross-over design at a dose of 5 mg/kg to 12 healthy ducks (six males and six females). Concentrations of the drug in serum were determined by a microbiological assay. The serum pharmacokinetic values for tobramycin were best represented using a one- or two-compartment open model, depending on the method of administration. Non-compartment analysis was also performed after IV administration. Tobramycin had a low degree of distribution and a relatively fast elimination. The mean volume of distribution in ducks (males and females) was higher than that reported in pigeons but lower than in chickens, with a slower rate of elimination. The IM injection resulted in a fast and complete absorption. The rate of elimination after IM administration was about twice as slow as in other avian species. Sex-related variations in tobramycin pharmacokinetics were similar to those reported for kanamycin and apramycin in hens and roosters.     

鸡源耐安普霉素大肠杆菌耐药表型研究

进行了安普霉素耐药大肠杆菌耐药表型的研究.采用常规方法和生化鉴定管对有过安普霉素用药史的鸡场分离的鸡源病原性大肠杆菌进行鉴定,并用试管二倍稀释法测定其最低抑菌浓度(MIC),筛选出鸡源安普霉素耐药大肠杆菌;采用药敏纸片法研究了这些耐药菌对安普霉素等14种抗菌药物的敏感性.共筛选出7株对安普霉素耐药的鸡源性大肠杆菌,这些耐药菌株全部对安普霉素、妥布霉素、奈啶酸、多西环素和阿莫西林耐药;大部分对庆大霉素、链霉素、卡那霉素、壮观霉素也呈现耐药.对新霉素的耐药较低,对阿米卡星高度敏感.部分交叉耐药现象的存在揭示对安普霉素等氨基糖苷类药物产生耐药性的菌株,其他抗生素也可能对它们失去疗效.     

Allometric scaling of orbifloxacin disposition in nine mammal species: a retrospective analysis

The objective of this study was to analyze the relationship between pharmacokinetic parameters and body weight (W) for orbifloxacin using reported pharmacokinetic data. The parameters of interest: clearance (Cl), volume of distribution at steady state (Vss) and elimination half-life were correlated across nine mammal species, including cattle, dog, rat, rabbit, goat, camel, horse, cat and sheep as a function of W using the conventional allometric equation Y = aW(b), where Y is the pharmacokinetic parameter, W is the body weight, a is the allometric coefficient (intercept) and b is the exponent that describes the relationship between the pharmacokinetic parameter and W. Our estimates (Cl=4.40 W(1.03); Vss=1.10W(1.05)) indicated that the increase in these parameters with W approximates a linear power relationship with slopes being very close to one. Overall, the results of this study indicated that it is possible to use allometry to predict pharmacokinetic variables of orbifloxacin based on W of mammal species.     

Antimicrobial resistance of Salmonella isolated from finishing swine and the environment of 60 Alberta swine farms

The study objective was to describe and evaluate antimicrobial resistance profiles in Salmonella isolated from Alberta swine finishing farms. Salmonella isolates (n = 322) were obtained from 192 fecal and 84 environmental samples of the 60 Salmonella-positive swine finishing farms. Isolates were classified susceptible, intermediate or resistant based on NCCLS guidelines. More than half of the isolates (53.4%) were susceptible to all of the 18 antimicrobials in the testing panel. No resistance was observed to amikacin, amoxicillin/clavulanic acid, cefoxitin, ceftiofur, ceftriaxone, cephalothin, ciprofloxacin, imipenem or nalidixic acid. Less than 1% of isolates were resistant to apramycin, gentamicin and trimethoprim/sulfamethoxazole. Higher frequencies of resistance were observed for chloramphenicol (4.7%), ampicillin (7.8%), kanamycin (11.8%), sulfamethoxazole (21.1%), streptomycin (25.5%) and tetracycline (38.8%). Eleven Salmonella serovars had isolates with resistance to > or =3 antimicrobials. The most frequently resistant serovar was Salmonella Derby, with 27 (38.0%) isolates resistant to > or =3 antimicrobials, including resistance to five and six antimicrobials. An absence of resistance to cephalosporins and fluoroquniolones and a low proportion of isolates resistant to amikacin, amoxicillin/clavulanic acid, apramycin, gentamicin and trimethoprim/sulfamethoxazole are encouraging findings from public health and animal health perspectives. Frequent resistance observed for ampicillin, kanamycin, sulfamethoxazole, streptomycin and tetracycline, antimicrobials commonly used in veterinary medicine for decades, indicates an urgent need to utilize these antimicrobials more prudently if their benefits are to be preserved.     

Interspecies variations in plasma half-life of ampicillin, amoxycillin, sulphadimidine and sulphacetamide related to variations in body mass.

The relationships between the half-lives during the elimination phase (t1/2 minutes) of ampicillin, amoxycillin, sulphadimidine and sulphacetamide and body mass (W, kg) between species of mammals and birds were examined using data from the authors' experiments and collected from the literature. Linear regression of the log half-lives of ampicillin, amoxycillin and sulphadimidine following intravenous injection on the log body mass for a variety of species of mammals and birds revealed significant correlations (r = 0.7709, n = 8, r = 0.7712, n = 8, r = 0.7749, n = 10). The interspecies relationships were described by the allometric equations t1/2 = 31.3 W0.16, t1/2 = 32.7 W0.12 and t1/2 = 129.2 W0.28, respectively. These equations may be of value for estimating dose intervals in species for which no relevant pharmacokinetic data are available.     

Allometric basis of enrofloxacin scaling in green iguanas

When body size varies greatly, drug disposition can best be described as an allometric function of body weight. Therefore, the allometry of standard metabolic rate (SMR; 3/4 power) and body surface area (BSA; 2/3 power) have been advocated as surrogate markers for the prediction of key pharmacokinetic parameters. The goal of the present study was to examine the allometric basis of pharmacokinetic scaling within a species, green iguanas. Enrofloxacin was administered intravenously to 20 green iguanas (322-3824 g), and noncompartmental analysis was used to calculate standard pharmacokinetic parameters, which were log(10) transformed and regressed against log(10) body weight. The slopes of significant regressions were compared with the values of unity, 3/4, and 2/3. The slope of enrofloxacin total body clearance (Cl) was also compared with the slopes relating SMR and renal Cl of (99m)Tc-diethylenetriamine penta-acetic acid ((99m)DTPA) to body weight in iguanas. Enrofloxacin Cl depended allometrically on body weight with the power of 0.32. The slope of enrofloxacin Cl was significantly less than those of SMR, Cl of (99m)DTPA, and the 2/3 value. Therefore, the relationship between enrofloxacin Cl and body weight does not directly depend on the allometry of BSA, SMR, or renal Cl of (99m)DTPA in iguanas.     

Pharmacokinetics of gentamicin in the calf: developmental changes

The purpose of this study was to determine the pharmacokinetic values for gentamicin in neonatal calves and to compare these values with those in adult cattle (cows). Gentamicin (4 mg/kg of body weight) was administered IV to 7 Holstein bull calves on days 1 (between 12 and 24 hours of age), 5, 10, and 15 after birth, and was administered once IV to 7 Holstein cows. Serum was collected from each animal before administration and at 22 different time intervals from 2 to 400 minutes after injection. Sera were analyzed for gentamicin concentrations. Decay of serum gentamicin concentrations was best described by a 2-compartment pharmacokinetic model. Elimination half-life (t1/2 (beta)) of gentamicin decreased from day 1 (149 minutes) to day 5 (119 minutes), but did not change between days 5 and 15 (111 minutes). Compared with the t1/2(beta) in 1- and 15-day-old calves, the t 1/2 (beta) in cows was shorter (76 minutes). In the calves, apparent volume of distribution (based on total area under the disposition curve) did not change between 1 (393 ml/kg) and 5 (413 ml/kg) days of age, decreased on day 10 (341 ml/kg) and cows day 15 (334 ml/kg), and was markedly smaller than that in cows (140 ml/kg). Total body clearance of gentamicin in cows (1.29 ml/min X kg) was lower than that seen in calves on day 1 (1.92 ml/min X kg) and on day 15 (2.10 ml/min X kg). The decrease in apparent volume of distribution of gentamicin was mirrored by a large decrease in the extracellular fluid volume, as measured by inulin space.(ABSTRACT TRUNCATED AT 250 WORDS)     

鸡源致病性大肠埃希菌中氨基糖苷类抗生素耐药基因的检测

为了解鸡源致病性大肠埃希菌对氨基糖苷类抗生素的耐药性变化和钝化酶耐药基因的携带情况及耐药基因与耐药性的相关性,从陕西、河南、河北、山西、宁夏和甘肃6省(区)的部分规模化养鸡场的病、死鸡中分离鉴定320株致病性大肠埃希菌。采用K-B药敏纸片法检测分离菌对6种氨基糖苷类药物的敏感性,PCR方法检测6种氨基糖苷类钝化酶耐药基因,用DNA Star软件对获得的耐药基因序列与GenBank中的相关序列进行比对。结果显示,鸡源致病性大肠埃希菌分离株对庆大霉素、链霉素、妥布霉素、卡那霉素、新霉素和阿米卡星的耐药率分别为53.4%、49.3%、37.5%、34.7%、22.8%和5.3%,对妥布霉素和卡那霉素耐药率呈上升趋势,而对庆大霉素的耐药率虽呈下降趋势,但仍维持在40%以上。3重以上耐药菌株占80%(256/320)。氨基糖苷类钝化酶基因aac(3)-Ⅱ、aph(3′)-Ⅰ和aac(6′)-Ⅰ的检出率分别为50.9%、25.9%和3.1%,未检测到aac(3)-Ⅳ、ant(3′′)-Ⅰ和aph(3′)-Ⅱ基因。研究表明,分离的鸡源致病性大肠埃希菌对氨基糖苷类抗生素的耐药性普遍存在,以多重耐药为主,且对妥布霉素和卡那霉素的耐药性不断上升。耐药基因aac(3)-Ⅱ和aph(3′)-Ⅰ的检出率与其耐药性呈正相关。     

犊牛大肠杆菌病病原的分离鉴定

从陕西杨凌某发病牛场采取腹泻犊牛病料5份,经微生物学诊断,从中分离出革兰阴性疑似致病菌6株。经生物学特性和生理生化试验鉴定,6株分离菌均为致病性大肠埃希菌。对分离菌进行抗生素敏感性试验,结果表明,该致病菌对氯霉素、菌必治、氧氟沙星、阿米卡星及卡那霉素等高度敏感;对妥布霉素、呋喃妥因和复达欣等中度敏感,对链霉素、庆大霉素、利福平、复方新诺明、四环素及红霉素等有较强的耐药性。动物致病性试验结果表明,该菌对小鼠有强致病性。     

Pharmacokinetics and intramuscular bioavailability of amikacin in chickens following single and multiple dosing

The pharmacokinetics of amikacin were studied in healthy mature female chickens (n = 6). Single doses of amikacin were injected as an i.v. bolus (10 mg/kg) and i.m. (20 mg/kg) into the same birds with a 30-day rest period between treatments. Amikacin was determined by the fluorescence polarization immunoassay method. The i.v. pharmacokinetics could be described by a two-compartment model with a t1/2 alpha of 0.150 +/- 0.064 h and a t1/2 beta of 1.44 +/- 0.34 h. The total body clearance was 0.109 +/- 0.017 1/h/kg and the volume of distribution at steady-state was 0.193 +/- 0.060 l/kg. Following a single i.m. injection, the peak plasma concentration (Cmax) was 50.79 +/- 4.05 micrograms/ml and occurred at 0.50 +/- 0.26 h. The i.m. extent of absorption was 91.2 +/- 17.6%. Simultaneous modeling of i.v. and i.m. results provided estimates of an absorption half-life of 0.480 +/- 0.158 h. The i.m. pharmacokinetics after repeated administration were studied following the tenth dose (20 mg/kg, every 8 h). The Cssmax was 38.58 +/- 6.96 micrograms/ml and occurred at 0.79 +/- 0.37 h, and the biological half-life of amikacin was 1.86 +/- 0.47 h. The multiple dosing yielded peak concentrations of 39 micrograms/ml and trough concentrations of 3.26 micrograms/ml. Based on these data, the recommended amikacin dosage in chickens is 20 mg/kg body weight every 8 h.     

Pharmacokinetics of gentamicin C1, C1a and C2 in horses after single intravenous dose

Gentamicin pharmacokinetics has not been studied in horses. Pharmacokinetics of gentamicin C1, C1a and C2 components following i.v. administration of total gentamicin at 6.6 mg/kg bwt to 6 healthy mature horses was determined. Significant differences in clearance, half-life (t 1/2), and mean residence time (MRT) between the gentamicin Cia and the 2 other components were found. The total body clearance (CL) of gentamicin C1a was 1.62 +/- 0.50 ml/min x kg and similar to the glomerular filtration rate (GFR) reported for horses. The CL of gentamicin C1 and C2 were 1.03 +/- 0.08 ml/min x kg and 1.10 +/- 0.15 ml/min x kg, respectively, and significantly slower than that of gentamicin C1a. The values of apparent volume of distribution at steady state were 0.22 +/- 0.05, 0.26 +/- 0.12 and 0.23 +/- 0.05 l/kg for gentamicin C1, C1a and C2, respectively. The MRT values were mean +/- s.d. 3.6 +/- 0.5, 2.7 +/- 0.3 and 3.5 +/- 0.4 h and the t 1/2 values were 3.1 (2.5-4.0), 2.4 (2.0-3.2) and 33 (2.4-4.3) h (harmonic mean and range) for gentamicin C1, C1a and C2, respectively. The MRT and t 1/2 values for gentamicin C1a were significantly shorter than those of gentamicin C1 and C2. It was concluded that the difference in pharmacokinetics between the gentamicin components has potential pharmacological and toxicological implications.