Raltegravir PK in blood plasma and the genital tract

Simon Collins, HIV i-Base

Jones and colleagues from University of North Carolina presented results of an open label single-arm pharmacokinetic study in seven HIV-negative women, comparing drug levels in blood plasma (BP) and cervical vaginal fluid (CVF) following standard dose raltegravir (400mg BID). [1]

Raltegravir was taken with a 545 kcal meal (18% fat, 70% carbs, 12% protein) and nine paired samples were taken on day one and day seven.

Although median levels achieved in CVF were 63% and ~100% of those in BP at day 1 and seven respectively (see Table 1), the IQR for the CVF:BP ratios showed such a wide interpatient variability crossing 1.0 that this couldnÂ’t be relied on for individual patient results [0.26-1.91 and 0.41-1.69 respectively].

Notably, elimination was slowed in CVF with a two-fold increase in half life (7 [5-12] vs. 17 [14-23] hours) compared to BP. Steady-state was reached after 2 days in BP and 4 days in CVF.

Table 1: Median [IQR] raltegravir levels in BP and CVF

Day 1
Cmax (ng/mL) 790 [249-2585] 631 [327-1658]
C12h (ng/mL) 55 [10-255] 607 [321-1283]
AUC 0-12h (ng*hr/mL) 3393 [717-7322] 1677 [910-66,716]
Tmax (hr) 6 [3-6] 12 [8-12]
Day 7
Cmax (ng/mL) 1874 [403-2200] 1272 [879-2388]
C12h (ng/mL) 19 [10-31] 282 [142-523]
AUC 0-12h (ng*hr/mL) 11,911 [6979-15,998] 9769 [2238-19,659]
Tmax (hr) 8 [6-12] 3 [0.5-3.0]


Bearing in mind these data are only showing IQR in a very small sample of women, the pharmacokinetics of raltegravir at steady state, show at least a 10-fold interpatient range in most parameters, in both BP and CVF.


Jones A et al. First-dose and steady-state pharmacokinetics (PK) of raltegravir in the genital tract of HIV uninfected women. 10th International Workshop on Clinical Pharmacology of HIV Therapy, 15-17 April 2009, Amsterdam. Oral abstract O-06.

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