Raltegravir PK in blood plasma and the genital tract
23 August 2009. Related: Conference reports, PK Workshop 10th 2009.
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 couldnt 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
| BP | 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] |
Comment
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.
Reference:
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.