Acceptable plasma concentrations of raltegravir and etravirine when administered by gastrostomy tube in a patient with advanced multidrug-resistant human immunodeficiency virus infection

Study objective: To determine whether the absorption of four antiretroviral agents-raltegravir, etravirine, emtricitabine, and tenofovir-is compromised when administered by gastrostomy tube.

Design: Pharmacokinetic analysis.

Setting: University medical center.

Patient: 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.

Measurements and main results: 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.

Conclusion: 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.