Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline.
The effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline was studied. In a randomized crossover design, six healthy male volunteers received an infusion of 200 mg of doxycycline hyclate on two occasions separated by 7 days. On one occasion, subjects were given 30 ml of aluminum hydroxide orally four times a day for 4 days, beginning 2 days prior to doxycycline dosing. Blood and urine samples were collected up to 48 and 96 h after the infusion, respectively, and were analyzed by a microbial assay. Values for volume of distribution at steady state, nonrenal clearance, urine recovery, and urine pH were not statistically different among treatment groups. With concomitant antacid therapy, the half-life of intravenous doxycycline was shortened from 16.2 +/- 2.6 to 11.2 +/- 1.2 h (P = 0.003), and total body clearance increased from 37.4 +/- 6.5 to 54.1 +/- 12.3 ml/min (P = 0.008). Area under the concentration-time curve for serum was decreased by 18 to 44%, with a 22 to 41% increase in renal clearance. Although the increase in nonrenal clearance ranged from 11 to 128%, the high variability led to a nonsignificant difference (P = 0.07). Concomitant oral antacid therapy may significantly enhance the clearance of intravenous doxycycline.
Nguyen
V X
VX
State University of New York, Buffalo School of Pharmacy.
Nix
D E
DE
Gillikin
S
S
Schentag
J J
JJ
D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000863:Antacids / Q000008:administration & dosage / Q000494:pharmacology*; D004318:Doxycycline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological
D000863:Antacids; D000536:Aluminum Hydroxide; D004318:Doxycycline