RESUMO
The pharmacokinetics of IV and oral cephradine in healthy young male and female volunteers (ages 19 to 25, n = 10) were compared to those of older individuals (ages 65 to 81, n = 9). Subjects received 1 gram of cephradine by a 5-minute intravenous (IV) infusion followed the next day by a 1-gram oral dose. Serial serum and urine samples collected over a period of 12 hours after the dose were analyzed for cephradine concentration by a microbiologic assay. After IV administration, mean serum cephradine concentrations in the elderly group were significantly higher at both 6 hours (1.52 +/- 0.41 mcg/mL) and 8 hours (0.73 +/- 0.22 mcg/mL) than in the young group at 6 hours (0.43 +/- 0.11 mcg/mL). Total systemic clearance was significantly lower (2.64 +/- 0.34 vs. 4.81 +/- 0.59 ml/min/kg) and the elimination half-life was significantly longer (1.71 +/- 0.20 vs 1.12 +/- 0.13 hours) in the elderly group (P = .0001). Systemic cephradine clearance correlated positively with creatinine clearance (r2 = 0.34, P = .0110) and negatively with age (r2 = 0.79, P = .0052). The mean volume of distribution was not significantly different between the two groups. Mean renal clearance was significantly lower in the elderly group (P = .0001), but more than 80% of the dose was excreted in the urine within 6 hours in both groups. After oral administration, the mean peak concentration and time to peak concentration did not differ between groups. The relative oral bioavailability was approximately 94% in both groups. The mean serum concentrations in the elderly were higher at both 6 and 8 hours than in the young group at 6 hours. There were no differences in pharmacokinetic parameters between male and female subjects. Because of reduced cephradine clearance secondary to an age-related decline in renal function, administration of cephradine every 8 hours, rather than every 6 hours, may be sufficient in elderly patients.
Assuntos
Cefradina/farmacocinética , Administração Oral , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Disponibilidade Biológica , Cefradina/administração & dosagem , Cefradina/sangue , Cefradina/urina , Feminino , Meia-Vida , Humanos , Infusões Intravenosas , Masculino , Taxa de Depuração Metabólica , Fatores de TempoRESUMO
Agranulocytosis is a rare but potentially lethal adverse effect of sulfasalazine. We report a case of sulfasalazine-associated agranulocytosis that occurred in a 79-year-old woman who had been taking the drug for approximately seven weeks. The patient had discontinued the drug on her own initiative nine days prior to admission. The patient was admitted with complaints of hoarseness, fever, odynophagia, and malaise. The total white blood cell count was 600/mm3 with a differential of 0% neutrophils, 8% bands, 67% lymphocytes, and 25% monocytes; a bone marrow aspirate and biopsy revealed maturation arrest. The patient's peripheral white blood cell count and differential progressively increased over the nine-day hospital course. Upon discharge the white blood cell count was 12,000 cells/mm3 with 66% neutrophils, 8% bands, 16% lymphocytes, and 10% monocytes. Complete blood counts should be performed periodically in patients receiving sulfasalazine, especially during the first two months of therapy. Pharmacists should counsel patients to discontinue the drug and consult their physician immediately if they develop unexplained fever, chills, sore throat, malaise, or other nonspecific illness during the initial two months of treatment.