Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem (L-627), in elderly subjects.
The pharmacokinetics and tolerability of a new parenteral carbapenem antibiotic, biapenem (L-627), were studied in healthy elderly volunteers aged 65 to 74 years (71.6 +/- 2.7 years [mean +/- standard deviation], n = 5; group B) and > or = 75 years (77.8 +/- 1.9 years, n = 5; group C), following single intravenous doses (300 and 600 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 well tolerated in all three age groups. Serial blood and urine samples were analyzed for biapenem to obtain key pharmacokinetic parameters by both two-compartment model-dependent and -independent methods. The maximum plasma concentration and area under plasma concentration-versus-time curve (AUC) increased in proportion to the dose in all three groups. Statistically significant age-related effects for AUC, total body clearance, and renal clearance (CLR) were found, while elimination half-life (t1/2 beta) and percent cumulative recovery from urine of unchanged drug (% UR) remained unaltered (t1/2 beta, 1.51 +/- 0.42 [300 mg] 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 A], 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 between 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 attributable to the combination of decreased lean body mass and lowered renal function of the elderly subjects. However, the magnitude of those changes does not necessitate dosage adjustment in elderly patients with normal renal function for their age.
Kozawa
O
O
Department of Pharmacology, Gifu University School of Medicine, Japan.
Uematsu
T
T
Matsuno
H
H
Niwa
M
M
Takiguchi
Y
Y
Matsumoto
S
S
Minamoto
M
M
Niida
Y
Y
Yokokawa
M
M
Nagashima
S
S
Kanamaru
M
M
D000328:Adult; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine
D015780:Carbapenems; D013845:Thienamycins; C065257:biapenem