PHARMACOKINETICS AND SAFETY OF A NEW PARENTERAL CARBAPENEM ANTIBIOTIC, BIAPENEM (L-627), IN ELDERLY SUBJECTS

The pharmacokinetics and tolerability of a new parenteral carbapenem a ntibiotic, biapenem (L-627), were studied in healthy elderly volunteer s aged 65 to 73 years (71.6 +/- 2.7 years [mean +/- standard deviation ], n = 5; group B) and greater than or equal to 75 years (77.8 +/- 1.9 years, n = 5; group C), following single intravenous doses (300 and 6 00 mg), and compared with those of healthy young male volunteers aged 20 to 29 years (23.0 +/- 3.5 years, n = 5; group A). The agent was wel l tolerated in all three age groups, Serial blood and urine samples we re analyzed for biapenem to obtain key pharmacokinetic parameters by b oth two-compartment model-dependent and -independent methods. The maxi mum plasma concentration and area under plasma concentration-versus-ti me curve (AUC) increased in proportion to the dose in all three groups . Statistically significant age-related effects for AUC, total body cl earance, and renal clearance (CLR) were found, while elimination half- life (t(1/2 beta)) and percent cumulative recovery from urine of uncha nged drug (% UR) remained unaltered (t(1/2 beta), 1.51 +/- 0.42 [300 m g] and 2.19 +/- 0.64 [600 mg] h [group A], 1.82 +/- 1.14 and 1.45 +/- 0.36 h [group B], and 1.75 +/- 0.23 and 1.59 +/- 0.18 h [group C]; %UR , 52.6% +/- 3.0% [300 mg] and 53.1% +/- 5.1% [600 mg] [group 4], 46.7% +/- 7.4% and 53.0% +/- 4.8% [group B], and 50.1% +/- 5.2% and 47.1% /- 7.6% [group C]), A significant linear correlation was observed betw een the CLR of biapenem and creatinine clearance at the dose of 300 mg but not at 600 mg, The steady-state volume of distribution tended to be decreased with age, although not significantly. Therefore, the age- related changes in parameters of biapenem described above were attribu table to the combination of decreased lean body mass and lowered renal function of the elderly subjects. However, the magnitude of those cha nges does not necessitate dosage adjustment in elderly patients with n ormal renal function for their age.