RESUMO
The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were evaluated after single and multiple oral doses of 250 and 500 mg of clarithromycin. Multiple-dose regimens used 12-hour dosing intervals for 7 doses. Plasma and urine concentrations were measured using high-performance liquid chromatography. Appearance of clarithromycin and its metabolite in plasma were rapid, as reflected by mean times to maximum plasma concentration ranging from 1.8 to 2.6 and 1.8 to 2.9 hours, respectively. The rises in clarithromycin peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) were disproportionate to increase in dose, suggesting nonlinearity in parent compound pharmacokinetics. Clarithromycin terminal disposition half-life (t1/2) also exhibited dose dependency, ranging from harmonic means of 2.7 to 4.8 hours. In contrast, based on Cmax AUC, and predicted/observed accumulation ratios, nonlinearity in metabolite pharmacokinetics was not observed. Plasma accumulation of metabolite occurred to a much lesser degree than that of the parent compound despite a substantially longer t1/2 for the metabolite (metabolite accumulation ratios based on AUC dose 7/AUC dose 1:250-mg regimen = 1.03 +/- 0.33, 500-mg regimen = 0.81 +/- 0.29, parent accumulation ratios: 250-mg regimen = 1.64 +/- 0.47, 500-mg regimen = 1.65 +/- 0.69). This would suggest that formation of this metabolite is capacity-limited and that this may in part account for the nonlinearity observed in clarithromycin pharmacokinetics. Urinary excretion constituted a relatively important route of elimination of clarithromycin, with renal clearance accounting for 17 to 31% of apparent total body clearance.
Assuntos
Claritromicina/farmacocinética , Administração Oral , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Claritromicina/administração & dosagem , Claritromicina/sangue , Claritromicina/urina , Esquema de Medicação , Meia-Vida , Humanos , Masculino , Taxa de Depuração MetabólicaRESUMO
One hundred three men undergoing thoracotomy on a general thoracic surgery service received endobronchial anesthesia with 100% oxygen using the Robertshaw tube. Bronchial intubation was accomplished in all. However, cross-leak or difficulty with deflation necessitated discontinuance in 8, while Pao2 values of 41 and 45 mm Hg caused abandonment in 2. There were no operative deaths. Surprisingly, hypoxemia in these patients related more to insufficient alveolar ventilation than to the venoarterial shunt.
