Effect of probenecid on pharmacokinetics of doripenem in healthy male volunteers
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Accession number;05A0663320
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| Title;Effect of probenecid on pharmacokinetics of doripenem in healthy male volunteers |
| Author;
SHIBA KOYA
(Tokyojikeikaiidai Naikagaku(kansenseigyobu))
NAKASHIMA MITSUYOSHI
(Hamamatsucptken)
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Journal Title;Japanese Journal of Chemotherapy
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Journal Code:F0608A
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ISSN:1340-7007
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VOL.53;NO.Supplement 1;PAGE.136-142(2005)
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| Figure&Table&Reference;FIG.2, TBL.4, REF.13 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;To determine the effects of probenecid on the renal excretion of doripenem (DRPM), a new carbapenem antibiotic for injection, we conducted an open-label, crossover (two-drug, two-period), single-dose study of DRPM in eight healthy male volunteers. DRPM was administered intravenously at a dose of 250 mg with or without probenecid. Concentrations in plasma and urine were determined to evaluate differences in pharmacokinetic profiles between two groups-one in which only DRPM was administered (DRPM group) and one in which DRPM was administered in combination with probenecid (DRPM/probenecid group). Pharmacokinetic parameters in the DRPM group were as follows: Cmax, 15.7 .+-. 2.8 .MU.g/mL; AUC, 17.10 .+-. 2.56 .MU.g h/mL; and half-life (t1/2), 0.94 .+-. 0.16 h. Pharmacokinetic parameters in the DRPM/probenecid group were as follows: Cmax, 18.1 .+-. 1.4 .MU.g/mL; AUC, 29.86 .+-. 2.10 .MU.g h/mL; and t1/2, 1.44 .+-. 0.11 h. The DRPM/probenecid group showed significant increases in Cmax and AUC (p=0.0091, p<0.0001), significant prolongation of t1/2 (p=0.0002), and a significant decrease in the following parameters: systemic clearance, 8.41 .+-. 0.58 L/h versus 14.91 .+-. 2.22 L/h in the DRPM group (p<0.0001); renal clearance, 5.52 .+-. 0.71 L/h versus 12.00 .+-. 2.21 L/h in the DRPM group (p=0.0001); and cumulative urinary excretion (0-12h), 65.8 .+-. 8.6% versus 80.4 .+-. 8.0% in the DRPM group (p=0.0017). These significant pharmacokinetic differences suggest that DRPM is excreted both by glomerular filtration and tubular secretion. (author abst.) |
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