Biomedical subjects

M Vousden

Publications and source records attributed to M Vousden.

At least 91 records · Page 5Linked to original sources

PubMedDate not supplied

Lack of pharmacokinetic interaction between gemifloxacin and digoxin in healthy elderly volunteers.

Gemifloxacin is a novel fluoroquinolone with a broad spectrum of antibacterial activity. The objective of this double-blind, randomized, placebo-controlled, 2-way crossover study was to demonstrate the lack of a pharmacokinetic interaction between gemifloxacin and digoxin. During two 14-day treatment periods, healthy elderly volunteers received digoxin (0.25 mg, once daily) co-administered on days 8-14 with either gemifloxacin (320 mg, p.o., once daily) or placebo. On day 14 of each period, blood samples and urine were collected for 24 h post dose and analysed for digoxin levels by radioimmunoassay. Steady-state digoxin pharmacokinetics were not affected by multiple dosing with gemifloxacin. There was no significant difference in digoxin values for the area under the plasma concentration-time curve over the dosing interval 0-24 h (AUC((0-24))) or the trough plasma concentration (C24) after co-administration with either gemifloxacin or placebo. Geometric means for AUC((0-24)) and C24 were 18.1 and 17.8 ng x h/ml and 0.597 and 0.566 ng/ml, respectively. The point estimates (90% confidence intervals) for AUC((0-24)) and C24 (digoxin + gemifloxacin):(digoxin + placebo) were 1.01 (0.93, 1.10) and 1.05 (0.95, 1.16), respectively, entirely within the equivalence range (0.80, 1.25). There were no marked differences between co-administration regimens for maximum observed plasma concentration (C(max)) or renal clearance values. Gemifloxacin was well tolerated during co-administration with digoxin, and the incidence of adverse events was similar to that seen with placebo. There were no clinically relevant changes in vital signs, electrocardiogram readings or laboratory parameters. In conclusion, this study demonstrates that gemifloxacin may be co-administered with digoxin without the need for digoxin dose adjustment.

Aged↗

PubMedDate not supplied

Effect of omeprazole on the pharmacokinetics of oral gemifloxacin in healthy volunteers.

This randomized, double-blind, 2-way crossover study investigated the effect of omeprazole on the pharmacokinetics of gemifloxacin, a novel fluoroquinolone. Thirteen healthy male volunteers received a 320 mg oral dose of gemifloxacin after 4 days of dosing with either omeprazole (40 mg once daily) or matching placebo. Blood was sampled for 48 h after dosing for determination of pharmacokinetic parameters. The mean area under the plasma concentration-time curve extrapolated to infinity (AUC(0-infinity)) and maximum plasma concentration (C(max)) for gemifloxacin were increased by, on average, 10% (90% confidence interval [CI], 0.89, 1.36) and 11% (90% CI, 0.87, 1.43), respectively, when gemifloxacin was given after omeprazole compared with after placebo. Neither the time to C(max) (T(max)) nor the half-life of gemifloxacin appeared to be affected by administration of omeprazole. There were no clinically relevant changes in adverse events, vital signs or the results of laboratory investigations after co-administration of omeprazole compared with placebo. In view of the modest increase in systemic exposure and the likely maximal increases indicated by the CIs, the effect of omeprazole on gemifloxacin pharmacokinetics is not considered to be clinically significant. Gemifloxacin and omeprazole can therefore be co-administered with no requirement for a dose adjustment.

Administration, Oral↗

PubMedDate not supplied

Effect of Maalox on the bioavailability of oral gemifloxacin in healthy volunteers.

This open, randomized, 4-way crossover study investigated the effect of the antacid Maalox on the bioavailability of gemifloxacin, a novel fluoroquinolone antimicrobial. Sixteen healthy male volunteers received gemifloxacin, 320 mg p.o., alone, 3 h after Maalox administration, or 10 min or 2 h before Maalox administration. Blood was sampled for 48 h after dosing to determine pharmacokinetic parameters. Estimates for the differences between regimens and 95% confidence intervals were calculated using the t-test for paired data. The administration of gemifloxacin 10 min before Maalox resulted in an average 85% reduction in the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)), whereas administration 3 h after Maalox produced a decrease in AUC(0-infinity), 15% of which was not considered to be clinically significant. The administration of gemifloxacin 2 h before Maalox had no notable effect on the gemifloxacin AUC(0-infinity) (average increase of 3%). Similar results were seen for the maximum gemifloxacin plasma concentration (C(max)). Neither the time to C(max) nor the half-life of gemifloxacin were notably altered by the administration of Maalox at any time relative to gemifloxacin dosing. There were no clinically important adverse experiences or changes in clinical laboratory parameters during this study. The findings of this study support the dosing recommendation that gemifloxacin can be administered either 2 h or more prior to, or 3 h or more after, the administration of Maalox.

Administration, Oral↗

PubMedDate not supplied

Evaluation of phototoxic potential of gemifloxacin in healthy volunteers compared with ciprofloxacin.

This double-blind, randomized, parallel-group comparative study investigated the phototoxic potential of gemifloxacin mesylate, a potent, novel fluoroquinolone antimicrobial. Forty healthy male and female volunteers received repeat dosing for 7 days with 160 mg or 320 mg of gemifloxacin (o.d., p.m.), 500 mg of ciprofloxacin (b.d.) or placebo (b.d.). On day 5 (large step) and day 6 (small step), graded series of wavebands were irradiated onto the back of each volunteer (phototesting). Skin reactions were assessed 0-30 min (immediate erythema) and 24 and 48 h (delayed erythema) after irradiation. Both gemifloxacin, 320 mg o.d., and ciprofloxacin, 500 mg b.d., were associated with mild phototoxicity following 7 days of administration. The range of mean phototoxic indices (the ratio of minimal erythemal dose at baseline compared with that on day 7 at the end of dosing) was 1.00-2.19 for gemifloxacin and 0.97-2.23 for ciprofloxacin. The abnormal responses occurred within the ultraviolet A region (335-365 +/-30 nm) and were maximal at 24 h. Susceptibility to phototoxicity had cleared 48 h after stopping the drug. The phototoxicity observed with gemifloxacin, 160 mg o.d., was lower than that at the higher dose and similar to that of placebo, suggesting that gemifloxacin phototoxicity is dose dependent. There were no clinically important changes in the safety profiles of gemifloxacin and ciprofloxacin compared with placebo in healthy volunteers after 7 days of repeat dosing. This study demonstrated that gemifloxacin, 320 mg o.d. given for 7 days, has a low potential to cause mild photosensitivity which is similar to that of ciprofloxacin, 500 mg b.d., given for the same period.

Adolescent↗

PubMedDate not supplied