Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction

Abstract

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.

Methadone: a review of drug-drug and pathophysiological interactions

“…The former is eliminated by hepatic metabolism and the latter has renal elimination. (71,72) Liver disease No effect Maintenance dosage need not be changed in stable chronic liver disease. A suggested explanation is that injury to the drug metabolizing system is offset by damage to the capacity of the liver to store and release unchanged methadone.…”

“…The interaction was unlikely as methadone and lamivudine were eliminated via different pathways. The former was eliminated by hepatic metabolism 21 , whereas the latter had renal elimination 72 . In a study of 14 patients who were coadministered methadone and zidovudine, serum zidovudine levels increased by 43% (p < 0.05) 73 .…”

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

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Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

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