Pharmacokinetic interactions of cefprozil with food, propantheline, metoclopramide, and probenecid in healthy volunteers.
Cefprozil, a new oral cephalosporin antibiotic, is composed of cis and trans isomers in an approximate 90:10 ratio. The objectives of this study were: (1) to assess the effects of alterations in gastrointestinal motility by metoclopramide and propantheline on the pharmacokinetics of cis and trans isomers of cefprozil, and to compare them with the effects of food on the pharmacokinetics of cefprozil; (2) to assess the effects of inhibition of renal tubular secretion by probenecid on the pharmacokinetics of cefprozil isomers. In this four-way crossover study, 15 healthy male volunteers received a 1000-mg dose of cefprozil after fasting, pretreatment with metoclopramide or propantheline, after breakfast, or after probenecid in an incomplete, balanced block design. There was a 1-week washout period between each treatment. Blood and urine samples collected over a 24-hour period were assayed for the cis and trans isomers. The concentrations of the trans isomers were generally 1/10 of the cis isomer. The means and variances of the pharmacokinetic parameters of the cis and trans isomers of cefprozil were similar in fasting subjects and were affected in a parallel manner by food, metoclopramide, propantheline, and probenecid. The pharmacokinetics of the cis isomer under the fasting condition were as follows: maximum peak plasma concentration (Cmax), 14.0 +/- 2.7 micrograms/mL; median time to reach Cmax (tmax), 1.5 (range, 1.0-3.5) hours; half-life (t1/2), 1.24 +/- 0.27 hours; area under the concentration (AUC0-infinity), 47.3 +/- 7.7 micrograms.hour/mL; mean residence time after oral administration (MRTpo), 2.9 +/- 0.4 hours; CLR, 219 +/- 60 mL/minute; and Xu% (percent cumulative urinary excretion in 0-24 hours), 68.1 +/- 12.5.(ABSTRACT TRUNCATED AT 250 WORDS)
Shukla
U A
UA
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Syracuse, New York 13221-4755.
Pittman
K A
KA
Barbhaiya
R H
RH
D000328:Adult; D002511:Cephalosporins / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005215:Fasting / Q000378:metabolism; D005502:Food; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007536:Isomerism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D011339:Probenecid / Q000494:pharmacology*; D011413:Propantheline / Q000494:pharmacology*; D000097670:Cefprozil
D002511:Cephalosporins; D008787:Metoclopramide; D011339:Probenecid; D011413:Propantheline; D000097670:Cefprozil