Stavudine Foods

The thymidine analog stavudine (d4T) (Figure 49-2) has high oral bioavailability (86%) that is not food-dependent. The serum half-life is 1.1 hours, the intracellular half-life is 3.0-3.5 hours, and mean cerebrospinal fluid concentrations are 55% of those of plasma. Excretion is by active tubular secretion and glomerular filtration (Table 49-... 

The oral bioavailability of stavudine in adults is 86%. Food does not interfere with its absorption. Peak plasma concentrations are reached within lh. The renal elimination accounts for 40% of its clearance. In addition to glomerular filtration, it undergoes active tubular secretion. Sixty percent of the remaining drug is eliminated by endogenous pathways. Its binding to plasma proteins is less than 5%. Stavudine in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. It causes suppression of HIV and sustained increase in CD4+ cells. 

Zidovudine may be taken irrespective of food and undergoes rapid first-pass hepatic metabohsm to 5-glucuronyl zidovudine. Patients initiating zidovudine treatment often complain of fatigue, malaise, myalgia, nausea, anorexia, headache, and insomnia, which generally resolve within the first few weeks of therapy. The mitochondrial toxicities shared by this class are commonly encountered. Stavudine and zidovudine compete for intracellular phosphorylation and should not be used together. 

Stavudine is well absorbed and its bioavailability is not affected by food. The dose should be adjusted in patients with renal insufficiency. A sustained-release formulation that can be given once daily is FDA-approved. 

Food can reduce the extent of absorption of didanosine, possibly causing a loss in efficacy. The extent of absorption of zalcitabine and zidovudine is reduced slightly by food. Food does not affect the extent of absorption of abacavir, emtricitabine, lamivudine, and stavudine. 

The UK manufacturer of stavudine notes that a standardised high-fat meal reduced, and delayed the time to reach the maximum plasma concentration (specific details not given), but did not alter the extent of systemic exposure of stavudine, when compared with the fasting state. Nevertheless, they recommend that, for optimal absorption, stavudine should be taken on an empty stomach at least 1 hour before meals. However, if this is not possible, they suggest giving stavudine with a light meal in addition the contents of the capsule may be mixed with food. The US manufacturer states that stavudine can be taken with food or on an empty stomach. ... 

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