Pharmacokinetics of amoxycillin in elderly in-patients.

The pharmacokinetics of amoxycillin (500 mg) given by intravenous injection and as two oral formulations on three consecutive days were investigated in eight frail elderly in-patients. Marked interindividual variation was found in all kinetic parameters after intravenous injection. The area under the curve (AUC) ranged from 32 to 155 mg.l-1.h and the distribution volume ranged from 13 to 37.1. The mean plasma clearance was 109 ml/min (range 53 to 255 ml/min). Elimination half-life ranged from 1.6 to 3.0 h (mean 2.4 h). The absolute bioavailability after oral administration was highly variable and ranged from 24 to 86% (mean 55%). The bioavailability of the two formulations was not significantly different. The performance of a pharmacokinetic study in these patients was very difficult, regarding their inability to tolerate an intravenous infusion, incontinence, disruption of everyday routine and problems with drinking the required volume of water.

Urinary concentrations of fosfomycin after a single 3 g dose of fosfomycin to elderly nursing-home patients.

The urinary concentrations of fosfomycin in 7 elderly patients with impaired renal function (mean creatinine clearance 40 ml/min) were studied after a single oral dose of 3 g fosfomycin as the trometamol salt. Urine samples were collected as 12 h portions for 84 h. Urinary concentrations of fosfomycin were 1,383 mg/l (range 314 to 4,200 mg/l) in the first 12 h and gradually declined to 165 mg/l (range 65 to 365 mg/l) between 36 and 48 h. 37% of the oral dose was recovered in the urine unchanged after 84 h, but a wide range (15-60%) in urinary recovery was observed. The elimination half-lives in the patients (estimated from the renal excretion profile of fosfomycin) ranged between 7 and 24 h. These data suggest that the urinary levels obtained in this patient population exceed the minimum inhibiting concentration of the usual pathogens involved in uncomplicated cystitis for at least 48 h. After 24 h the urinary concentrations of fosfomycin are higher than those reported for healthy young subjects.