AEGiS-Glasgow [PL6.3a] Effect of atazanavir on intracellular and plasma pharmacokinetics of saquinavir and ritonavir administered once-daily in HIV infected patients

Seventh International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 14-17 November 2004

[PL6.3a] EFFECT OF ATAZANAVIR ON INTRACELLULAR AND PLASMA PHARMACOKINETICS OF SAQUINAVIR AND RITONAVIR ADMINISTERED ONCE-DAILY IN HIV INFECTED PATIENTS

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL6.3a

Jennifer Ford¹, Marta Boffito², Adrian Wildfire², Andrew Hill³, David Back¹, Saye Khoo¹, Mark Nelson², Graeme Moyle², Brian Gazzard², Anton Pozniak²
¹Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool; ²PK Research Ltd, St Stephen's Centre, Chelsea and Westminster Hospital, London; ³Roche Products Ltd, Hertfordshire, Welwyn Garden City, UK

There are no data on the impact of atazanavir (ATV) on intracellular (IC) pharmacokinetics of saquinavir (SQV) or ritonavir (RTV). We have examined IC and plasma SQV and RTV concentrations with and without co-administration of ATV.

SQV/RTV concentrations PBMCs and plasma were determined in nine HIV patients on SQV/RTV 1600/100 mg QD. Blood was collected (2, 6, 12, 24h). Plasma and IC exposure (AUC_0-24h) were assayed by HPLC-MS/MS and accumulation ratios calculated. The same HIV patients also received SQV/ATV/r 1600/200/100 mg to steady state and concentrations determined to examine ATV effects on SQV/RTV. Studies were performed 10 months apart.

Median plasma SQV exposure was significantly increased (11.5 to 27.0 mg.h.L^-1) With ATV (P = 0.004). In these 9 patients, no change in median RTV plasma exposure was seen (7.4 to 6.4 mg.h.L^-1). Median IC SQV AUC_0-24h was significantly increased (34.9 to 117.2 mg.h.L^-1) with ATV (P = 0.004). No change in IC RTV exposure was noted (9.5 to 12.9 mg.h.L^-1). C_min of SQV in plasma and cells was higher with ATV (SQV plasma C_min 49.4 to 143.6 ng.ml^-1, P = 0.02; SQV IC C_min 605.4 to 2026.5 ng.ml^-1, P = 0.02). No change in acumulation ratio of SQV or RTV was noted.

ATV increased both plasma and IC exposure (AUC_0-24h) and Cmin of SQV but not RTV. Addition of ATV to a QD SQV/RTV regimen maybe useful for patients with SQV concentrations below the minimum effective concentrations, however further efficacy studies are warranted.

SESSION 6: RESISTANCE AND PHARMACOKINETICS

2004-11-14
PL6-3a

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