The effect of mixing the contents of efavirenz capsules (sprinkles) with a small amount of food on the bioavailability and pharmacokinetics of efavirenz in healthy adults was evaluated.
In a randomized, three-period, crossover study, 24 healthy adult subjects were divided equally into two groups. Group I received treatments A, B, and C, and those in group II received treatments A, D, and E. Treatment A was three efavirenz 200-mg intact capsules under fasting conditions. Treatments B, C, D, and E were three efavirenz 200-mg capsule contents mixed with two teaspoons of applesauce, grape jelly, yogurt, or infant formula, respectively. A single dose was given on days 1, 21, and 41. The steady-state mean maximum observed concentration, time of maximum observed concentration, area under the concentration-time curve (AUC) half-life, taste, and safety were assessed.
The AUC after administration of a single 600-mg dose of efavirenz sprinkles mixed with two teaspoons of any of the food vehicles to healthy adults was bioequivalent to a 600-mg efavirenz dose given as intact capsules under fasting conditions. Subjects rated efavirenz mixed with grape jelly as the most palatable. Adverse events and laboratory abnormalities were similar for all treatments.
The AUC of efavirenz 600 mg administered as capsule sprinkles with two teaspoons of applesauce, grape jelly, yogurt, or infant formula was bioequivalent to a single dose of efavirenz 600 mg given as intact capsules under fasting conditions in healthy adults.
[Show abstract][Hide abstract] ABSTRACT: To determine whether the absorption of four antiretroviral agents-raltegravir, etravirine, emtricitabine, and tenofovir-is compromised when administered by gastrostomy tube.
University medical center.
A 52-year-old African-American man coinfected with advanced multidrug-resistant human immunodeficiency virus (HIV) and chronic hepatitis B, who was receiving treatment with raltegravir, etravirine, emtricitabine, and tenofovir, and developed ulcerative esophagitis with perforation, requiring a gastrostomy tube.
Due to the patient's esophageal perforations, all nutrition and drug therapy had to be provided by gastrostomy tube. As his antiretroviral regimen of raltegravir, etravirine, and emtricitabine-tenofovir was not available in liquid or powder formulations, the oral tablets were crushed or dispersed and mixed with water, then administered by gastrostomy tube. To ensure that the absorption of the drugs was sufficient for antiretroviral response, plasma samples were collected at 2 hours and 12 hours after dosing, and drug concentrations were quantitated by using validated assays. The 2- and 12-hour postdose plasma concentrations were 1220 and 446 ng/ml for raltegravir, 212 and 274 ng/ml for etravirine, 1148 and 164 ng/ml for emtricitabine, and 320 and 94 ng/ml for tenofovir, respectively. The patient's plasma concentrations were then compared with those in published pharmacokinetic studies of oral regimens administered to HIV-infected persons and healthy volunteers. Overall, the plasma concentrations of the antiretrovirals administered by gastrostomy tube were similar to published values. No drug toxicities were observed in this patient.
These pharmacokinetic data suggest that absorption of raltegravir, etravirine, emtricitabine, and tenofovir was not compromised when the drugs were administered by gastrostomy tube. These findings provide a basis for further investigation of the pharmacokinetics, safety, tolerance, and antiretroviral response to raltegravir, etravirine, and emtricitabine-tenofovir when the oral route of administration is not possible.
[Show abstract][Hide abstract] ABSTRACT: Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. 80% of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m(2) . Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV -33%, EFV -15%, ritonavir -17%) compared to well-nourished controls [p < 0.001], attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% [p < 0.001], whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure [p < 0.001], explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority.
The Journal of Clinical Pharmacology 02/2014; 54(2). DOI:10.1002/jcph.167 · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), used for the treatment of human immunodeficiency virus (HIV)-1 infection. Approved by the US Food and Drug Administration in 1998, its indication was recently extended to include children as young as 3 months of age. The World Health Organization and many national guidelines consider efavirenz to be the preferred NNRTI for first-line treatment of children over the age of 3 years. Clinical outcomes of patients on three-drug antiretroviral regimens which include efavirenz are as good as or better than those for patients on all other currently approved HIV medications. Efavirenz is dosed once daily and has pediatric-friendly formulations. It is usually well tolerated, with central nervous system side effects being of greatest concern. Efavirenz increases the risk of neural tube defects in nonhuman primates and therefore its use during the first trimester of pregnancy is limited in some settings. With minimal interactions with antituberculous drugs, efavirenz is preferred for use among patients with HIV/tuberculosis coinfection. Efavirenz can be rendered inactive by a single point mutation in the reverse transcriptase enzyme. Newer NNRTI drugs such as etravirine, not yet approved for use in children under the age of 6 years, may maintain their activity following development of efavirenz resistance. This review highlights key points from the existing literature regarding the use of efavirenz in children and suggests directions for future investigation.
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