1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP
October 25 - 29, 2003 Warsaw, Poland
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9TH EUROPEAN AIDS CONFERENCE (EACS) 1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP October 25 - 29, 2003 Warsaw, Poland |
| 4.1 PK and Pharmacodynamics F2/4 - INDINAVIR PLASMA EXPOSURE IS NOT AFFECTED BY RITONAVIR/LOPINAVIR CO-ADMINISTRATION IN A BOOSTED DOUBLE PI-ONLY THERPAY REGIMEN |
| (1) Pharmazentrum Frankfurt, J.W.Goethe-University Hospital, Frankfurt, Germany,2 Medical HIV Treatment and Research Unit, J.W.Goethe-University Hospital, Frankfurt, Germany,3 Internal Medical Practice Grueneburgweg, Frankfurt, Germany,4 THERAPIA GmbH, AVK-Hospital, Berlin, Germany |
Background: For HIV-patients who have lost their treatment options with reverse transcriptase inhibitors (RTI), a protease-inhibitor (PI) only regimen could be a treatment alternative. The co-administration of Saquinavir and Lopinavir/Ritonavir (LPV/r) has already been shown as a possible salvage therapy regimen.
Objectives: We investigated the potential pharmacokinetic interaction of a boosted double PI regimen of Lopinavir/Ritonavir (LPV/r) plus Indinavir (IDV).
Methods: We determined 12-h plasma drug levels of IDV, LPV and RTV in HIV-1 infected adult patients, taking IDV 800mg plus LPV/r 399/99mg BID only and compared the results to patients with LPV/r 399/99mg BID (plus 2 or 3 nucleoside RTI). The results were evaluated by a non-compartmental 2-stage approach and in addition a pre-defined 2-compartmental model (TOPFIT 2.0®).
Results: The addition of LPV to a IDV/RTV therapy regimen does not affect the IDV Area under the curve under steady state conditions (AUCss) despite significantly lower RTV plasma levels. The non-compartmental results are presented in the table.
| Treament (group) | n | AUCss (ng12h/ml) | Cmax (ng/ml) | Cmin (ng/ml) |
| median (range) | median (range) | median (range) | ||
| IDV (A) | 15 | 37290(19384-49975) | 5290(3120-6900) | 824(295-1780) |
| LPV (A) | 15 | 72420(47715-117200) | 7170(4740-11200) | 4650(1440-6320) |
| RTV (A) | 15 | 4203(1750-6506)* | 583(344-679)* | 135(36-283)* |
| IDV (B) ² | 14 | 42381(18254-63320) | 5610(3150-9360) | 690(247-3390) |
| RTV (B) ² | 14 | 12569(3922-26771) | 1365(493-4280) | 376(124-871) |
| LPV (C) ² | 13 | 69440(37240-158000) | 7740(4250-16300) | 3790(946-9460) |
| RTV (C) ² | 13 | 2794(853-4520)** | 424(94-830)** | 77(44-224)*** |
| ² co-administration of 2 or 3 NRTI * p<0,005; ** p< 0,0001 (Mann-Whitney U-test: compared to RTV in the IDV/RTV group (B) All statistics were performed by BIAS 7.06 ® |
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Conclusion: The comparison of the RTV plasma exposure in all groups is indicating, that even low RTV plasma levels sufficiently booster IDV or LPV. A dose adjustment of IDV, co-administrated with LPV/r in a double-PI regimen is not necessary.
Presenting Author: Nils Von Hentig, J.W.Goethe-University, Pharmazentrum, Theodor-Stern-Kai 7, 60590, Frankfurt/M., Germany, Phone: 0049-69-63017622
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