This single-dose, randomized, crossover study was carried out to investigate the potential effect of ranitidine on the pharmacokinetics of chlorpheniramine. The study also afforded an opportunity to add to the limited data currently available on the stereoselective pharmacokinetics of chlorpheniramine. Healthy subjects received a single oral 4 mg dose of racemic chlorpheniramine on two separate occasions: alone, and on day 6 of dosing with ranitidine 75 mg b.i.d. for 8 days. Serum concentrations and urinary recovery of (S)-(+)- and (R)-(-)-chlorpheniramine were unaffected by administration of ranitidine, indicating no pharmacokinetic drug-drug interaction. The observed chlorpheniramine pharmacokinetic data were consistent with previous data and indicated approximately 2.5-fold higher serum concentrations of the (S)-(+) enantiomer. Previously reported high variability in chlorpheniramine pharmacokinetics was greatly reduced by well-controlled food and fluid intake.

The pharmacokinetics of single doses of cefaclor at 250 and 375 mg and cefuroxime axetil at 250 mg administered under optimal conditions (i.e., cefuroxime axetil after food and cefaclor in the fasted state) were studied in 24 healthy male volunteers. Drug concentrations in serum were related to MICs for common respiratory tract pathogens by using data generated from a recently completed national survey. The time the concentrations in serum exceeded the MICs for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (formerly BranhameUla) catarrhalis were significantly greater (P < 0.05) for cefuroxime axetil at 250 mg than for cefaclor at 250 or 375 mg. With the recommended dosing regimens (cefuroxime axetil at 250 mg and cefaclor at 375 mg twice daily or cefaclor at 250 mg three times daily), cefuroxime concentrations exceed the MIC for 90% of the strains tested for a greater time period than cefaclor concentrations with either regimen. The reasons for this difference are (i) the greater potency and slower clearance of cefuroxine compared with those of cefaclor and (ii) the greater sensitivity of these pathogens to cefuroxime.

1The pharmacokinetics of bismuth and ranitidine derived from ranitidine bismuth citrate given in single oral doses ranging from 200 mg to 1600 mg were evaluated in healthy subjects. 2Bismuth was only minimally absorbed (<0.5% of the amount dosed) after administration of ranitidine bismuth citrate, and peak plasma concentrations never exceeded 33 ng ml−1 in any subject. Plasma concentrations and urinary recoveries of bismuth at doses up to and including 800 mg were relatively constant and not proportional to dose. Bismuth absorption was increased more than proportionally with the dose at 1600 mg. 3The pharmacokinetics of ranitidine after administration of ranitidine bismuth citrate were dose‐proportional and consistent with previous observations for ranitidine administered alone. 4Ranitidine bismuth citrate was well‐tolerated in single oral doses of up to 1600 mg.

These data indicate that the current recommendation for renal impairment dose reduction (by two-thirds when Ccr < 50 m1-min-1) might result in under-treating moderately impaired patients, and suggests a less conservative dose reduction (by half when Ccr < 10 m1.min-1) to avoid therapeutic failure while remaining within the wide margin of safety for this drug.

No abstract