didanosine and Kidney-Failure--Chronic

To evaluate the pharmacokinetics of didanosine in patients with normal kidney function or chronic kidney failure.. Three groups of patients with human immunodeficiency virus (HIV) infection were studied: group I, six men with normal kidney function (creatinine clearance > 90 ml/min/1.73 m2); group II, six men with chronic renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD); and group III, four men and two women with chronic renal failure receiving hemodialysis three times a week. A 300 mg dose of didanosine was administered orally and intravenously according to a two-period randomized crossover design. Patients in group III were studied between hemodialysis sessions during the crossover periods. In addition, patients in group III were studied in a third period after administration of a 300 mg oral dose of didanosine 4 hours before hemodialysis.. After intravenous administration in group I, the mean (+/-SD) total clearance (CLT) was 13.0 +/- 1.6 ml/min/kg and the elimination half-life (t 1/2) was 1.56 +/- 0.43 hour. In groups II and III, the CLT decreased significantly to 3.4 +/- 1.2 and 3.2 +/- 1.2 ml/min/kg, respectively, whereas the t1/2 increased to 3.60 +/- 0.82 hours and 3.11 +/- 0.88 hours, respectively. The absolute bioavailability of didanosine in groups I, II, and III was 42% +/- 12%, 52% +/- 6%, and 38% +/- 11%, respectively, and did not differ significantly. CAPD had little effect on the removal of didanosine, whereas approximately 30% of the drug present in the body at the start of dialysis was eliminated by an average 3-hour dialysis session.. The clearance of didanosine is impaired in patients with chronic renal failure. To compensate, the dose and schedule of administration should be adjusted. It is recommended that one-fourth of the total daily dose of didanosine be administered once a day in this patient population.

Topics: Administration, Oral; Adult; Anti-HIV Agents; Dialysis; Didanosine; Female; HIV Seropositivity; Humans; Injections, Intravenous; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Reference Values

Information on antiretroviral dosing errors among health care providers for outpatient human immunodeficiency virus (HIV)-infected patients is lacking. We evaluated factors associated with nucleoside reverse-transcriptase inhibitor dosing errors in a university-based HIV clinic using an electronic medical record. Overall, older age, minority race or ethnicity, and didanosine use were related to such errors. Impaired renal function was more common in older patients and racial or ethnic minorities and, in conjunction with fixed-dose combination drugs, contributed to the higher rates of errors in nucleoside reverse-transcriptase inhibitor dosing. Understanding the factors related to nucleoside reverse-transcriptase inhibitor dosing errors is an important step in the building of preventive tools.

Topics: Adult; Age Factors; Cohort Studies; Didanosine; Drug Combinations; Drug Prescriptions; Ethnicity; Female; HIV Infections; Hospitals, University; Humans; Internship and Residency; Kidney Failure, Chronic; Male; Medical Audit; Medical Records Systems, Computerized; Medication Errors; Nurse Practitioners; Outpatient Clinics, Hospital; Practice Guidelines as Topic; Reverse Transcriptase Inhibitors

Topics: Adult; Aluminum; Didanosine; Humans; Kidney Failure, Chronic; Male; Renal Dialysis