RESUMO
The disposition of coadministered ticarcillin (3 g/1.73 m2) and clavulanic acid (100 mg/1.73 m2) was examined after a 30-min infusion in 24 noninfected subjects with various degrees of renal function. Noncompartmental pharmacokinetic parameters for the individual compounds were determined from plasma concentrations and urinary excretion rates. All clearances (total, renal, and nonrenal) and urinary recoveries of unchanged drug were found to be linearly related to creatinine clearance (CLCR). The steady-state volume of distribution (9.9 and 12.9 liters for ticarcillin and clavulanic acid) approximated the extracellular fluid space and was not related to CLCR. The half-lives increased with reduced renal function and ranged from 56 to 392 min for ticarcillin and 26 to 266 min for clavulanic acid. The clearances of both drugs decreased proportionately with reduction in renal function, facilitating dosing adjustments based on CLCR. Calculations of expected steady-state maximum and minimum concentrations in plasma using constant doses and an extended dosing interval related to CLCR further rationalized use of the 30:1 drug combination ratio for all patients.
Assuntos
Ácidos Clavulânicos/metabolismo , Nefropatias/metabolismo , Rim/metabolismo , Penicilinas/metabolismo , Ticarcilina/metabolismo , Adolescente , Adulto , Ácidos Clavulânicos/farmacologia , Ácidos Clavulânicos/urina , Combinação de Medicamentos/metabolismo , Combinação de Medicamentos/farmacologia , Combinação de Medicamentos/urina , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Nefropatias/fisiopatologia , Cinética , Pessoa de Meia-Idade , Ticarcilina/farmacologia , Ticarcilina/urina , Inibidores de beta-LactamasesRESUMO
The ratio of the peak serum concentration after a 500-mg dose of amikacin to the pathogen minimum inhibitory concentration was determined for 95 patients under treatment for serious Gram-negative infections. There were 113 such ratios. The relationship of this inhibitory ratio to the clinical effectiveness and side effects of treatment with this new aminoglycoside was also studied. Mean peak serum concentration of drug was 25.8 microgram/ml, and mean inhibitory ratio was 13.0. Ninety-six per cent of inhibitory ratios were greater than or equal to 1.0. Therapy was rated totally effective in 85% of patients clinically evaluated and partially effective in 3%. Signs of renal or eighth cranial nerve impairment attributable to drug administration were confined to only two patients, and there were no other side effects. The reliability of amikacin therapy appears to be related to dependable serum levels and high inhibitory ratios.
