Pharmacokinetics of the cephalosporin SM-1652 in mice, rats, rabbits, dogs, and rhesus monkeys

Matsui, Hiroki; Yano, Koji; Okuda, Takuo

doi:10.1128/aac.22.2.213

Cited by 37 publications

(26 citation statements)

References 7 publications

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“…In the present study, the percentage of the dose of CPM excreted into the bile obtained in 20-week-old healthy SDRs (58%) was consistent with the value (60%) obtained in healthy SDRs reported previously (18). We found marked decreases in the CL bile of CPM in EHBRs; the CL bile values of CPM dropped in 10-and 20-week-old EHBRs to 1/7 and 1/15, respectively, of that in healthy SDRs, although the differences between the two EHBR groups failed to reach the 5% level of statistical significance.…”

Section: It Is Known That the Biliary Excretion Of Organic Anions Is supporting

confidence: 93%

“…On the other hand, nonbiliary and nonrenal clearances for CPM did not change among the three groups and contributed little to the elimination of CPM from the body (6 to 12% of CL sys ). It has been reported that CPM is almost completely recovered in the urine and bile in the unchanged form (Ͼ90%) and that the amount of its metabolite that is recovered is negligible (18). The results from the present study also indicate that the increased urinary excretion of CPM in EHBRs compensates for a reduction in the biliary excretion ability, although this compensation is not complete.…”

Section: It Is Known That the Biliary Excretion Of Organic Anions Is supporting

confidence: 66%

“…It has also been reported that the uptake of CPM into the membrane vesicles is strongly inhibited in a competitive manner by ␤-lactam antibiotics known to be mainly excreted into bile (1,29,35). For these reasons, CPM was selected as a model drug for studying ␤-lactam antibiotics because it is excreted into the bile at high concentrations (18) and possesses a relatively low affinity and high capacity for the carrier systems in bile canalicular membranes (29). To better understand the effect of the biliary excretion dysfunction in EHBRs on the pharmacokinetic behaviors of drugs, we investigated the pharmacokinetic characteristics of CPM, in particular, the biliary and urinary excretions of CPM in 10-and 20-week-old EHBRs, and compared the findings with those for 20-week-old healthy SDRs.…”

Section: It Is Known That the Biliary Excretion Of Organic Anions Is mentioning

confidence: 99%

“…CPM has been shown to be eliminated mainly into the bile in unchanged form by active biliary secretion in both humans and animals (18,22,31), suggesting that CPM could be prescribed as the preferred drug for the treatment of hepatobiliary infections. Some studies support the biliary excretion mechanism of CPM and the effect of obstructive jaundice on its pharmacokinetic behavior in experimental animals (13,29).…”

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confidence: 99%

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Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats

Muraoka

Hasegawa

Nadai

et al. 1995

Antimicrob Agents Chemother

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Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbilirubinemia were recently derived from Sprague-Dawley rats (SDRs). The pharmacokinetic characteristics of the ␤-lactam antibiotic cefpiramide (CPM), which is mainly excreted into bile, were investigated in 10-and 20-week-old EHBRs and were compared with those in 20-week-old healthy SDRs. The pharmacokinetic parameters of CPM after an intravenous administration of 20 mg/kg of body weight were estimated for each rat by noncompartmental methods. When compared with age-matched healthy SDRs, significant decreases (by approximately 30%) in the systemic clearance of CPM were observed in 20-week-old EHBRs. The biliary clearance of CPM in 20-week-old EHBRs markedly decreased to less than 10% of that in age-matched healthy SDRs, while total urinary recovery of unchanged CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of CPM were observed between the two groups of EHBRs. There were no significant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubinemia induces an increase in the urinary excretion ability of CPM in return for a reduction in the biliary excretion.Hyperbilirubinemia in rats is known to modify the pharmacokinetics of certain drugs as a result of the impairment of the process of biliary excretion (13,25,26,30). Hyperbilirubinemic mutant TR Ϫ and GY rats derived from Wistar strain rats have generally been used as experimental animal models for hyperbilirubinemia because they exhibit abnormalities in the biliary excretion of various organic anions and glucuronided and sulfated bile acids, which are similar to the symptoms of DubinJohnson syndrome in humans (8,11,16,24).Eisai hyperbilirubinemic mutant rats (EHBRs), which possess much higher concentrations of conjugated bilirubin in plasma, were derived from Sprague-Dawley rats (SDRs) (7,19). Several investigators have recently reported that hyperbilirubinemia in EHBRs decreases the biliary secretion of various organic anions by impairing the canalicular membrane transport (26,28) and that the canalicular membrane vesicles isolated from EHBRs and TR Ϫ rats lack the ATP-dependent canalicular transport capability of organic anions (6, 9). These observations suggest that the biliary secretory characteristics of organic anions in EHBRs closely resemble those in TR Ϫ and GY rats (6,26,28) and in humans with Dubin-Johnson syndrome (4). Thus, EHBRs can be used as an animal model for studying hyperbilirubinemia in humans.Cefpiramide (CPM), an anionic ␤-lactam antibiotic, exhibits antibacterial activity against gram-positive and gram-negative bacteria, in particular, to Pseudomonas aeruginosa, which is resistant to several antibiotics. CPM has been shown to be eliminated mainly into the bile in unchanged form by active biliary secretion in both humans and animals (18,22,31), suggesting that CPM could be prescribed as the preferred drug for the ...

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Section: It Is Known That the Biliary Excretion Of Organic Anions Is supporting

confidence: 93%

Section: It Is Known That the Biliary Excretion Of Organic Anions Is supporting

confidence: 66%

Section: It Is Known That the Biliary Excretion Of Organic Anions Is mentioning

confidence: 99%

mentioning

confidence: 99%

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Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats

Muraoka

Hasegawa

Nadai

et al. 1995

Antimicrob Agents Chemother

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“…It is highly protein bound (96.3% at 100 pg/ml) and has a reported half-life of 4.4 h in volunteers with normal renal function (6,7). High and prolonged concentrations in blood are achieved after intravenous infusion.…”

mentioning

confidence: 99%

Pharmacokinetics of cefpiramide in volunteers with normal or impaired renal function

Conte

1987

Antimicrob Agents Chemother

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The pharmacokinetics of a single 2.0-g intravenous dose of cefpiramide in patients with normal or impaired renal function were studied. Serial concentrations in serum and urine were measured by using highperformance liquid chromatography, and the effect of the concentration in serum on protein binding was assessed. Thirty patients (ten with creatinine clearances of >80 mi/min, ten with creatinine clearances between 10 and 80 ml/min, and ten on dialysis) were studied. The concentration-time curve of cefpiramide was best described by an open two-compartment model. The elimination half-lives in patients with normal or impaired renal function or those on dialysis were 5.41 ± 1.44, 8.3 ± 2.82, and 8.38 ± 4.06 h, respectively, and the serum clearances in the same groups were 2.0 ± 0.84, 1.29 ± 0.45, and 2.04 ± 1.10 liters/h, respectively. There were no significant differences in any of the parameters among the three groups of patients. In patients with normal or impaired renal function, protein binding varied between 93.0 ± 1.3% at 304.4 ,ug/ml and 99.3 ± 0.8% at 41.1 ,ug/ml and was linearly and inversely related to the cefpiraniide concentration in serum. In patients on dialysis, protein binding was significantly lower (P < 0.05) and varied between 88.5 ± 7.1% at 173.4 ,ug/ml to 94.9 ± 4.8% at 46.8 ,ug/ml. In patients with normal or abnormal renal function, renal cefpiramide clearance decreased linearly with declining renal function, whereas plasma clearance was maintained. Therefore, nonrenal elimination becomes more important as renal impairment progresses.

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Interspecies scaling: prediction of human biliary clearance and comparison with QSPKR

Morris

Yang

Gandhi

et al. 2012

Biopharm & Drug Disp

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The aim of this study was to evaluate the prediction performance of various allometric scaling methods in predicting human biliary clearance (CL(b)) from data in rats or multiple animal species and to compare the prediction performance with that of quantitative structure pharmacokinetic relationship (QSPKR) models. CL(b) data of parent drugs in rats and humans were collected from the literature for 18 compounds. A simple allometric approach was applied to CL(b) or unbound CL(b) using 0.75 or 0.66 as the allometric exponent. For scaling from rat studies alone, the prediction using 0.66 as the exponent was better than that using 0.75, and a better prediction was obtained for unbound CL(b) than CL(b). For a subset of compounds, six multiple-species scaling methods were compared, with the best prediction achieved with the simple unbound CL(b) approach. However, in the absence of protein binding data, the correction with maximum life-span potential (MLP) or 'Rule of exponent' (ROE) method offered the best prediction. Overall, multiple species had better predictability than scaling with the rat alone. Comparison of predicted human CL(b) values using multiple animal species and QSPKR offered similar prediction performance. In conclusion, the results of the present study, although based on limited data, suggested that the prediction for human CL(b) by allometry was greatly improved by the incorporation of protein binding. Human CL(b) prediction using rat data alone was not satisfactory. Additionally, QSPKR provides an alternative approach to allometry for the prediction of human biliary clearance.

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Pharmacokinetics of the cephalosporin SM-1652 in mice, rats, rabbits, dogs, and rhesus monkeys

Cited by 37 publications

References 7 publications

Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats

Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats

Pharmacokinetics of cefpiramide in volunteers with normal or impaired renal function

Interspecies scaling: prediction of human biliary clearance and comparison with QSPKR

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