Gastric emptying and the pharmacokinetics of the cephalosporin antibiotic, cefpodoxime proxetil.
The effects of gastric motility on the pharmacokinetics of cefpodoxime proxetil, an oral, broad spectrum, third-generation cephalosporin antibiotic were evaluated in 12 healthy subjects. In this open-label, crossover trial, each subject took a 200 mg dose (two 100 mg film-coated tablets) in each study period. There was an initial fasting period followed by a control period and then either a propantheline or metoclopramide period. Gastric motility was measured using [99mTc]-labeled sulfur colloid in oatmeal in the control, propantheline and metoclopramide periods. Treatment with propantheline or metoclopramide was given 30 min before dosing with the antibiotic and the radioisotope. Serial images with a gamma counter were made every 15 min for 2 h. Gastric emptying time was faster than control with metoclopramide, but generally slower with propantheline than control. The mean peak plasma concentration, mean area under plasma concentration time curve and mean half-life of cefpodoxime proxetil were similar in all groups as compared to control. The mean time to peak plasma concentration was delayed in the propantheline period and peak plasma concentrations were greater at all sampling times at six hours after dosing. This study utilized the gastric nuclear scan with modification of gastric motility by metoclopramide and propantheline and with simultaneous determination of the disposition of cefpodoxime proxetil to understand the absorption of the drug.
Hughes
G S
GS
Upjohn Research Clinic, Upjohn Company, Kalamazoo, Michigan.
Heald
D L
DL
Patel
R
R
Spillers
C R
CR
Batts
D H
DH
Euler
A R
AR
D000293:Adolescent; D000328:Adult; D001681:Biological Assay; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005746:Gastric Emptying; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D011413:Propantheline / Q000494:pharmacology; D011532:Providencia / Q000187:drug effects; D011877:Radionuclide Imaging; D013270:Stomach / Q000000981:diagnostic imaging; D013671:Technetium Tc 99m Sulfur Colloid; D000097627:Cefpodoxime Proxetil
D015296:Ceftizoxime; D008787:Metoclopramide; D011413:Propantheline; D013671:Technetium Tc 99m Sulfur Colloid; D000097627:Cefpodoxime Proxetil