7th Conference - Abstract 82

Pilot Study of BID and TID Combinations of Saquinavir-SGC (S), Delavirdine (D), Zidovudine (ZDV) & Lamivudine (3TC) as Initial Therapy: Pharmacokinetic (PK) Interaction between S-SGC and D

S. COX*¹, B. CONWAY², W. FREIMUTH¹, E. BERBER³, L. PAXTON¹, B. CAREL¹, L. NIETO⁴, C. RIVERA⁵, M. WOLFF⁶, J. BENETUCCI⁷, P. CAHN⁸, and K. WILLIAMS⁹ for the 0081 Study Group. ¹Pharmacia & Upjohn, Kalamazoo, MI; ²Univ. of British Columbia & Viridae Clin. Sci., Vancouver; ³Pharmacia & Upjohn, Mississauga, ON, Canada; ⁴Hosp. Gen. Gabriel Mancera IMSS, Mexico, D.F.; ⁵Hosp. Gen. de Mexico, D.F.; ⁶Hosp. San Borja Arriaran, Santiago, Chile; ⁷Hosp. Muniz, Buenos Aires; ⁸Fndn. Huesped, Buenos Aires, Argentina; and ⁹Royal Univ. Hosp., Saskatoon, SK, Canada

Introduction: A previous study showed that D increases systemic exposure to S following administration of S-HGC. This study was undertaken to evaluate the PK interaction between D and S following co-administration with S-SGC (Fortovase).
Methods: Treatment naïve HIV-1 infected pts with baseline plasma viral load >5,000 cps/mL were randomized to receive one of four combination regimens: S-SGC, 3TC & D administered bid (Group I) or tid (Group II) vs. S/3TC/D/ZDV bid (Group III) vs. S/3TC/ZDV tid (Group IV). Full PK studies were performed at Wk 4, and plasma was assayed for S and D by LC/MS/MS. Average steady-state concentration (Css) was calculated as AUC_0-t/t, where t is the dosing interval. Oral clearance (CL/F) was calculated as dose/AUC_0-t. PK parameters from Groups I & III were pooled.
Results: Mean (SD) values of PK parameters are listed below (n=9-10 for each group):

D inhibited S CL/F (p<.05) and marginally increased the S Css (p<.1), as seen by comparing Group IV to the other groups. The S Cmin from Group II was marginally higher than the values from the other groups (p<.1). D parameters from the bid and tid groups were not different (p>.1).
Conclusions: Combination therapy of S-SGC with D allows the use of a lower total daily dose of S-SGC in a bid regimen with no reduction in S systemic exposure. Systemic D exposure is similar between the 600mg bid and 400mg tid regimens.

Key Words: Delavirdine, Pharmacokinetics, Saquinavir