AEGiS-13IAC: Can saliva be used as an alternative specimen for therapeutic drug monitoring (TDM) of nevirapine (NVP) in HIV-1-infected patients?

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Can saliva be used as an alternative specimen for therapeutic drug monitoring (TDM) of nevirapine (NVP) in HIV-1-infected patients?

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB542)

Van Heeswyk R, Veldkamp AI, Mulder JW, Meenhorst PL, Beynen JM, Lange JM, Hoetelmans RM
R. Van Heeswyk, Slotervaart Hospital Dept Pharmacy, Louwesweg 6, 1066 EC Amsterdam, Netherlands, Tel.: +312 051 244 81, Fax: +312 051 247 53, E-mail: aprom@slz.nl

BACKGROUND: TDM of NVP may be helpful to detect patient non-compliance or subtherapeutic exposure to this drug. Traditionally, plasma (PL) is used for TDM. We explored if the concentration of NVP in saliva (SA) is an indicator of the corresponding concentration in PL, to evaluate the applicability of SA for TDM of NVP. Design: The steady-state pharmacokinetics of NVP in PL and SA were assessed in HIV+ patients who used NVP 200 mg bid to explore the relationship between the concentration of NVP in PL and SA. Paired PL and stimulated SA (Salivette é «) samples were obtained just before and 1, 2, 3, 4, 5, 6, 8, 10, and 12 h post ingestion of NVP. To validate the anticipated relationship prospectively, single, paired PL and SA samples were obtained from NVP-treated HIV+ patients who attended the outpatient clinic for our routine antiretroviral drug monitoring program. Concentrations of NVP in PL and SA were measured with a sensitive and validated HPLC assay.

RESULTS: In total, 12 HIV+ patients participated in the full pharmacokinetic evaluation of NVP. The PL NVP concentrations ranged from 2.5 to 15 mg/L (median 5.2 mg/L) and were highly significantly correlated with the SA concentrations (r = 0.89, p > 0.001). The ratio of the NVP concentration in SA and PL (SA/PL ratio) was independent of time (p = 0.53). The mean ( é SD) SA/PL ratio was 0.51 ( é 0.083). The intra-and interpatient variability of the SA/PL ratio was 15.3 and 5.4%, respectively. Single, paired PL and SA samples were obtained from 32 outpatients. For these patients, the mean ( é SD) percentage deviation of the predicted PL NVP concentration, based on the SA concentration, from the observed PL concentration, was -7.2% ( é 14.0).

CONCLUSION: Our data suggest that SA may be used as an alternative for PL, for TDM of NVP.

Keywords: AEGIS, Nevirapine, HIV-1, HIV Infections, Saliva, Drug Monitoring, Antiretroviral Therapy, Highly Active, HIV-1 Reverse Transcriptase, HIV Seropositivity, Human, therapy, drug therapy
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