OBJECTIVES: Data suggest that some licensed antiretroviral doses could be reduced. We assessed the safety, tolerability and pharmacokinetics of lopinavir/ritonavir at doses of 400/100, 200/150 and 200/50 mg twice daily in HIV-negative volunteers (http://clinicaltrials.gov/ct2/show/NCT00985543). METHODS:Male and female volunteers were administered lopinavir/ritonavir at doses of 400/100 mg (two lopinavir/ritonavir Meltrex 200/50 mg tablets, Regimen 1), 200/150 mg (one Meltrex tablet, one 100 mg ritonavir capsule, Regimen 2) and 200/50 mg (one Meltrex tablet, Regimen 3). Each dose was given twice daily for 7 days sequentially, separated by a 7 day wash-out period. Lopinavir/ritonavir steady-state pharmacokinetics was assessed over 12 h at the end of each phase (days 7, 21 and 35). Pharmacokinetic parameters were compared using the 400/100 mg twice daily dose as reference, by determining geometric mean ratios (GMRs) and 90% confidence intervals. RESULTS:Twenty-two subjects (eight females) completed the study. Lopinavir AUC(0-12) (ng h/mL), C(max) (ng/mL) and the minimum concentration (C(trough)) (ng/mL) for the 400/100, 200/150 and 200/50 mg twice daily doses, respectively, were as follows: 99,599, 73,603 and 45,146; 11,965, 8939 and 6404; and 5776, 4293 and 1749. Lopinavir pharmacokinetic parameters were significantly lower for Regimens 2 and 3: GMR (90% CI) AUC(0-12), 0.74 (0.65-0.84) and 0.45 (0.40-0.51); C(max), 0.75 (0.66-0.85) and 0.54 (0.40-0.60); and C(trough), 0.74 (0.62-0.89) and 0.30 (0.25-0.36), respectively. All subjects taking the 400/100 and 200/150 mg twice daily doses, and 19 (86%) subjects taking 200/50 mg twice daily had lopinavir concentrations above the suggested minimum effective concentration of 1000 ng/mL. CONCLUSIONS: These pharmacokinetic data show that therapeutic plasma concentrations of lopinavir can be achieved with 200/150 mg of lopinavir/ritonavir twice daily (one Meltrex tablet and one 100 mg ritonavir capsule twice daily).
RCT Entities:
OBJECTIVES: Data suggest that some licensed antiretroviral doses could be reduced. We assessed the safety, tolerability and pharmacokinetics of lopinavir/ritonavir at doses of 400/100, 200/150 and 200/50 mg twice daily in HIV-negative volunteers (http://clinicaltrials.gov/ct2/show/NCT00985543). METHODS: Male and female volunteers were administered lopinavir/ritonavir at doses of 400/100 mg (two lopinavir/ritonavir Meltrex 200/50 mg tablets, Regimen 1), 200/150 mg (one Meltrex tablet, one 100 mg ritonavir capsule, Regimen 2) and 200/50 mg (one Meltrex tablet, Regimen 3). Each dose was given twice daily for 7 days sequentially, separated by a 7 day wash-out period. Lopinavir/ritonavir steady-state pharmacokinetics was assessed over 12 h at the end of each phase (days 7, 21 and 35). Pharmacokinetic parameters were compared using the 400/100 mg twice daily dose as reference, by determining geometric mean ratios (GMRs) and 90% confidence intervals. RESULTS: Twenty-two subjects (eight females) completed the study. Lopinavir AUC(0-12) (ng h/mL), C(max) (ng/mL) and the minimum concentration (C(trough)) (ng/mL) for the 400/100, 200/150 and 200/50 mg twice daily doses, respectively, were as follows: 99,599, 73,603 and 45,146; 11,965, 8939 and 6404; and 5776, 4293 and 1749. Lopinavir pharmacokinetic parameters were significantly lower for Regimens 2 and 3: GMR (90% CI) AUC(0-12), 0.74 (0.65-0.84) and 0.45 (0.40-0.51); C(max), 0.75 (0.66-0.85) and 0.54 (0.40-0.60); and C(trough), 0.74 (0.62-0.89) and 0.30 (0.25-0.36), respectively. All subjects taking the 400/100 and 200/150 mg twice daily doses, and 19 (86%) subjects taking 200/50 mg twice daily had lopinavir concentrations above the suggested minimum effective concentration of 1000 ng/mL. CONCLUSIONS: These pharmacokinetic data show that therapeutic plasma concentrations of lopinavir can be achieved with 200/150 mg of lopinavir/ritonavir twice daily (one Meltrex tablet and one 100 mg ritonavir capsule twice daily).
Authors: B G Gazzard; Jane Anderson; Abdel Babiker; Marta Boffito; Gary Brook; Gary Brough; Duncan Churchill; Ben Cromarty; Satyajit Das; Martin Fisher; Andrew Freedman; Anna Maria Geretti; Margaret Johnson; Saye Khoo; Clifford Leen; Devaki Nair; Barry Peters; Andrew Phillips; Deenan Pillay; Anton Pozniak; John Walsh; Ed Wilkins; Ian Williams; Matthew Williams; Mike Youle Journal: HIV Med Date: 2008-10 Impact factor: 3.180
Authors: Laura Else; Victoria Watson; John Tjia; Andrew Hughes; Marco Siccardi; Saye Khoo; David Back Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2010-04-09 Impact factor: 3.205
Authors: Marta Boffito; Laura Else; David Back; Jessica Taylor; Saye Khoo; Marta Sousa; Anton Pozniak; Brian Gazzard; Graeme Moyle Journal: Antivir Ther Date: 2008
Authors: Daniel González de Requena; Francisco Blanco; Teresa Garcia-Benayas; Inmaculada Jiménez-Nácher; Juan González-Lahoz; Vincent Soriano Journal: AIDS Patient Care STDS Date: 2003-09 Impact factor: 5.078
Authors: Scott Wick; David I Walsh; Johanna Bobrow; Kimberly Hamad-Schifferli; David S Kong; Todd Thorsen; Keri Mroszczyk; Peter A Carr Journal: ACS Synth Biol Date: 2019-04-30 Impact factor: 5.110
Authors: Ricardo Moure; Pere Domingo; Joan Villarroya; Laura Gasa; José M Gallego-Escuredo; Tania Quesada-López; Samantha Morón-Ros; Alberto F Maroto; Gracia M Mateo; Joan C Domingo; Francesc Villarroya; Marta Giralt Journal: Antimicrob Agents Chemother Date: 2018-05-25 Impact factor: 5.191
Authors: Marco Siccardi; Catia Marzolini; Kay Seden; Lisa Almond; Anna Kirov; Saye Khoo; Andrew Owen; David Back Journal: Clin Pharmacokinet Date: 2013-07 Impact factor: 6.447
Authors: A Dravid; T P Betha; A K Sharma; R Gawali; U Mahajan; M Kulkarni; C Saraf; S Kore; M Dravid; N Rathod Journal: HIV Med Date: 2020-07-20 Impact factor: 3.180