Saliva as an Alternative Body Fluid for Therapeutic Drug Monitoring of the Nonnucleoside Reverse Transcription Inhibitor Nevirapine

Abstract

The objective of this study was to evaluate the applicability of saliva as an alternative body fluid for therapeutic drug monitoring of nevirapine. The pharmacokinetics of nevirapine in plasma and saliva during a dosing interval was assessed in HIV-1-infected patients taking nevirapine (200 mg twice daily) to explore the relation between the concentration of nevirapine in plasma and saliva. To validate the anticipated relationship prospectively, single, paired plasma and saliva samples were obtained from nevirapine-treated HIV-1-infected outpatients. The plasma nevirapine concentration was strongly correlated with the salivary concentration. The mean saliva/plasma concentration ratio was 0.51 and was independent of the time after ingestion. Salivary nevirapine concentrations were used to estimate the corresponding plasma concentrations for 31 outpatients. Compared with the true plasma concentrations, the estimated concentrations were biased by -4.2%, with a precision of 13.3%. These data show a strong correlation between the salivary and plasma concentrations of nevirapine at a dosage of 200 mg twice daily. This relation has been validated prospectively, and the prediction of plasma concentrations was accurate and precise. Therefore, the authors conclude that saliva can be a useful body fluid for therapeutic drug monitoring of nevirapine.

Determination of salivary efavirenz by liquid chromatography coupled with tandem mass spectrometry

“…Determination of EFV levels in human hair [7] and reports of determining nevirapine [8,10] and indinavir [24] from saliva have been published, but this study is the first validated LC-MS/MS method for the assay of EFV in saliva to be reported.…”

“…Therapeutic drug monitoring (TDM) of antiretroviral (ARV) plasma concentrations can be useful in the optimization of HIV treatment [6,7], however, the collection of plasma is invasive, causes discomfort and is painful [8] especially in young children, opposed to the collection of saliva which can be done by noninvasive, painless methods and has a diminished risk of HIV transfer to the health care worker [8]. However, for the use of saliva for TDM, a confirmed relationship should exist between the concentrations of the drug in the different body fluid matrixes [8].…”

“…However, for the use of saliva for TDM, a confirmed relationship should exist between the concentrations of the drug in the different body fluid matrixes [8]. An obstacle for the determination of EFV in saliva, is the protein binding of EFV, which is greater than 99% [1].…”

“…Saliva usually represents the free drug concentration of a drug [9], thus the salivary concentrations are very low (<1% of plasma levels). Methods to determine salivary levels of nevirapine [8,10] and indinavir [11] were previously reported, but none yet for EFV. To further investigate the possibility of assaying salivary EFV to monitor adherence or for therapeutic drug monitoring of EFV, a validated analytical LC-MS/MS based method for the analysis of EFV in saliva, was developed.…”

Evaluation of Saliva as an Alternative Matrix for Monitoring Plasma Zidovudine, Lamivudine and Nevirapine Concentrations in Rwanda

“…Few studies investigated the use of saliva for therapeutic drug monitoring (TDM) and/or compliance control studies in HIV infected patients undergoing antiretroviral therapy (HAART) [3][4][5][6]. Rolinski and collaborators have shown a good correlation between plasma and salivary concentrations of zidovudine (ZDV) in ten HIV-infected patients suggesting that stimulated saliva might be an appropriate specimen for ZDV-TDM [3].…”