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• W2121649929 abstract "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 μg/mL; median time to reach Cmax (tmax), 1.5 (range, 1.0–3.5) hours; half-life (t 1/2), 1.24 ± 0.27 hours; area under the concentration (AUC0-∞), 47.3 ± 7.7 μg · hour/mL; mean residence time after oral administration (MRTpo), 2.9 ± 0.4 hours; CLB, 219 ± 60 mL/minute; and Xu% (percent cumulative urinary excretion in 0–24 hours), 68.1 ± 12.5. Propantheline delayed the tmax and significantly increased the MRTpo of the cefprozil isomers, relative to the fasting state, but other pharmacokinetic parameters were not significantly altered. Metoclopramide reduced the tmax and significantly decreased the MRTpo of both isomers of cefprozil, but other pharmacokinetic parameters were not significantly altered. Food slightly delayed the tmax but did not have a significant effect on other pharmacokinetic parameters of either isomer. Pretreatment with probenecid resulted in a significant increase in the t1/2, Cmax, AUC0-∞, and MRTpo, and in a significant decrease in the CLR of each isomer, indicating that probenecid competitively inhibits renal tubular secretion of cefprozil. In summary, the extent of absorption of cefprozil was not affected by drugs that change gastric motility nor by concurrent administration of food. Probenecid significantly decreased the renal clearance and prolonged the t1/2 of cefprozil, indicating that renal tubular secretion is a significant pathway in elimination of cefprozil." @default.
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• W2121649929 title "Pharmacokinetic Interactions of Cefprozil With Food, Propantheline, Metoclopramide, and Probenecid in Healthy Volunteers" @default.
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• W2121649929 doi "https://doi.org/10.1002/j.1552-4604.1992.tb03876.x" @default.
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