Hextall A, Radley S, Andrews J M, Boyd E J, Dent J C, Donovan I, Wise R
Department of Surgery, Dudley Road Hospital, Birmingham, UK.
J Antimicrob Chemother. 1994 Mar;33(3):595-602. doi: 10.1093/jac/33.3.595.
Each of 12 patients undergoing routine diagnostic upper gastrointestinal endoscopy received a single iv infusion of clindamycin phosphate 300 mg over 10 min. During the endoscopy, mucosal biopsies of the gastric antrum and fundus were obtained at varying times following the infusion. The clindamycin concentrations in the biopsies and in serum samples also taken after the infusion were determined. In addition, six healthy volunteers participated in a cross-over study on two different days. On both days, each subject received a single iv infusion of clindamycin phosphate 300 mg, immediately after which, gastric secretion was stimulated by iv pentagastrin (2 micrograms/kg/h) which was infused continuously over 150 min. On one of the study days, acid secretion by the stomach was inhibited by a slow iv infusion of ranitidine 50 mg. Clindamycin concentrations in gastric aspirates and serum samples collected after the infusion were determined. Concentrations of clindamycin in the fundal mucosa were significantly higher than the simultaneous serum concentrations (median ratio of tissue concentration to serum concentration, 2.0; P < 0.005) while concentrations in the antral mucosa were similar to those in serum (median ratio, 1.2; P = 0.65). Ranitidine significantly inhibited pentagastrin-stimulated acid secretion as demonstrated by a decrease in the volume of gastric aspirate when ranitidine was administered compared with when it was not administered (P < 0.01). Clindamycin concentrations in gastric juice were approximately one and one-half times higher than those in serum samples obtained simultaneously, both during stimulation of gastric acid secretion with pentagastrin and during inhibition of pentagastrin-stimulated acid secretion with ranitidine. Gastric juice concentrations of clindamycin were significantly higher following administration of ranitidine than after stimulation of gastric secretion by pentagastrin alone. Fundal mucosal and gastric juice concentrations of clindamycin exceeded the hypothetical maximum serum concentrations, indicating that accumulation in the stomach occurred against a concentration gradient.
