RESUMEN
OBJECTIVE: To characterize the pharmacokinetics of a single 500 mg oral dose of famciclovir in subjects with varying degrees of renal impairment. METHODS: Twenty-seven subjects were enrolled in an open-label parallel-group study. Eighteen patients had renal impairment (average age [ +/- SD], 49 +/- 12 years), and nine subjects were healthy volunteers (average age, 28 +/- 7 years). Patients with renal impairment were stratified into groups based on estimated creatinine clearance (CLCR): mild impairment (CLCR, 60 to 80 ml/min/1.73 m2), moderate impairment (CLCR, 30 to 59 ml/min/1.73 m2) and severe impairment (CLCR, 5 to 29 ml/min/1.73 m2). Plasma and urine specimens were analyzed for concentrations of penciclovir, the antivirally active metabolite of famciclovir, by reverse-phase HPLC. Plasma data were analyzed with use of model-independent methods. RESULTS: In subjects with normal renal function (CLCR > 80), the mean maximum plasma concentrations of penciclovir was 2.83 micrograms/ml (range, 1.30 to 3.82 micrograms/ml) and the mean time to reach maximum concentration was 0.89 hours (range, 1/2 to 1 1/2 hours). The mean apparent terminal elimination half-life was 2.15 hours (range, 1.56 to 2.87 hours). A linear relationship was observed between the plasma elimination rate constant and CLCR and between renal clearance and CLCR. Mean area under the plasma concentration-time curve from zero to infinity was approximately tenfold higher and the plasma elimination rate constant was approximately fourfold lower in patients with severe renal impairment than in subjects with normal renal function. CONCLUSION: Consideration should be given to modification of the dosing schedule of famciclovir from the usual 8-hour interval to a 12-hour interval for patients with moderate renal impairment (CLCR 30 to 59 ml/min/1.73 m2) or a 24-hour interval for patients with severe renal impairment (CLCR < 30 ml/min/1.73 m2).
Asunto(s)
2-Aminopurina/análogos & derivados , Enfermedades Renales/metabolismo , Profármacos/farmacocinética , 2-Aminopurina/administración & dosificación , 2-Aminopurina/sangre , 2-Aminopurina/farmacocinética , 2-Aminopurina/orina , Administración Oral , Adulto , Anciano , Cromatografía Líquida de Alta Presión , Creatinina/sangre , Creatinina/orina , Famciclovir , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Growth hormone-releasing peptide (GHRP, SK&F 110679) is a hexapeptide (His-DTrp-Ala-Trp-DPhe-LysNH2) that selectively stimulates the release of growth hormone (GH) but not other pituitary hormones in vitro and in vivo in a variety of animal species. GHRP was administered to 17 normal men at doses of from 0.05 to 2.5 micrograms/kg as a 30 min intravenous infusion. Eight of the men were infused with saline as a control. Serum GH increased consistently at doses of 0.25 microgram/kg and above during the infusion of the peptide, peaked at 45 min and then decreased to baseline values by 210 min. The mean peak serum GH concentrations (+/- SE) in response to GHRP infusion were 17.8 +/- 6.1 micrograms/L at a dose of 0.25 microgram/kg (n = 4, p = .03 vs saline), 38.3 +/- 9.2 micrograms/L at 0.5 microgram/kg (n = 4, p = .04 vs saline) and 63.0 +/- 5.4 micrograms/L at 1.0 microgram/kg (n = 4, p = .002 vs saline). Serum LH, FSH, TSH and ACTH were unaffected by GHRP administration. GHRP was safe and well-tolerated in all men. GHRP infusion resulted in a dramatic, selective and dose-dependent increase in serum GH concentrations.