Metabolism antiretroviral drugs

The majority of antiretroviral medications are metabolized by the cytochrome P-450 enzyme system (CYP). Therefore, it is important to review patient medication profiles for drugs that may interact with antiretroviral drugs. 

After oral administration, abacavir is rapidly absorbed, and its bioavailability is about 83%. Food does not interfere with its absorption, and it is metabolized by alcohol dehydrogenase to 5 -carboxylic acid derivative and to S -glucuronidc by glucuronidation. Abacavir does not affect the cytochrome P-450 system. In combination with other antiretroviral drugs, abacavir is indicated for the treatment of HIV-1 infection. It is more potent than other nucleoside reverse transcriptase inhibitors in reducing HIV plasma concentration and increasing CD4+ count. 

Levothyroxine is metabolized in part through the action of glucuronyl transferase, which can be inhibited by some antiretroviral drugs, such as indinavir. 

Fichtenbaum CJ, Gerber JG. Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. Clin Pharmacokinet 2002 41 1195-1211. 

An important consideration in the use of all HIV-1 protease inhibitors, but of ritonavir in particular, is their potential for drug interactions through their effects on cytochrome P450 isozymes. The various interactions of ritonavir with other antiretroviral drugs have been reviewed (139). Ritonavir, which inhibits CYP2D6, the principal pathway by which MDMA is metabolized, can also produce clinically relevant interactions with recreational drugs (140). 

Nevirapine is used in combination with at least two other antiretroviral drugs, usually for progressive or advanced HIV infection, although it appears effective also in pregnancy. It penetrates the CSF weU, and undergoes hepatic metabolism (t) 28 h). It is taken once daily, increasing to twice daily if rash is not seen. Rash and hepatitis are the commonest side effects. 

Antiretroviral drugs In 12 healthy HIVnegative volunteers, nelflnavir reduced plasma methadone concentrations by 40-50%, increased its renal clearance, and increased hepatic metabolism, extraction, and clearance [96 ]. 

Lipodystrophy is a feature of treatment with antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors. It has been attributed to inhibition of mitochondrial DNA polymerase y [53 ]. It is associated with other metabolic alterations, such as lactic acidosis, dyslipide-mia, and insulin resistance, and may in turn be associated with an increase in the longterm risk of cardiovascular diseases [54, 55 ]. It causes loss of fat from the face and limbs and can be accompanied by accumulation of fat in the trunk and the back of the neck. It affects up to 50% of the patients taking highly active antiretroviral drug treatment (HAART). 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

Drugs that may induce metabolism of CHC and reduce efficacy (griseofulvin, antiretroviral History of ectopic pregnancy... 

Itraconazole has significant interactions with a number of commonly prescribed drugs, such as rifampin, phenytoin, and carbamazepine. Itraconazole raises serum digoxin and cyclosporine levels and may affect the metabolism of oral hypoglycemic agents and coumadin. Absorption of itraconazole is impaired by antacids, Hj blockers, proton pump inhibitors, and drugs that contain buffers, such as the antiretroviral agent didanosine. 

Due to first-pass metabolism, if administered alone lopinavir has varied plasma levels. This problem is overcome by adding ritonavir to the formulation. Its oral absorption is rapid, and its bioavailability is increased by food rich in fat content. Lopinavir is metabolized by cytochrome P-450 isoenzyme CYP3A4. Most of the drug in the plasma is bound to ai-acid glycoprotein. In combination with other antiretroviral agents, lopinavir is indicated for the treatment of HIV infection. 

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