OBJECTIVES: To assess whether the neurological or gastrointestinal adverse effects of ritonavir correlate with parameters of ritonavir systemic exposure. METHODS: Peak (Cmax) and trough (Cmin) ritonavir plasma levels were compared in 11 patients experiencing side-effects (group A) versus 10 patients without side-effects (group B). Ritonavir was administered with the following escalation dosing scheme: 300, 400, 500 mg twice a day for 3, 4, and 5 days, respectively, then the full dose of 600 mg twice a day. Blood sampling was done in group A within 24 h of the occurrence of side-effects and in group B after at least 3 days of the full dosage regimen. RESULTS: Both Cmax and Cmax were significantly higher (Mann-Whitney U test) in patients with side-effects. Cmax was [median (interquartile range)] 26.7 (22.7-33.3) mg/l versus 16.2 (13.4-17.0) mg/l (P = 0.001) and Cmin was 12.6 (9.1-13.9) versus 7.5 (4.9-8.6) mg/l (P = 0.002). CONCLUSION: Patients with higher ritonavir concentrations are at a higher risk of experiencing neurological or gastrointestinal side-effects. Individualization of the dosage regimen, e.g. a downward titration of the ritonavir dose in patients with side-effects, guided by plasma level monitoring, may result in a substantial increase in the percentage of patients tolerating ritonavir without increasing the risk of treatment failure as a result of suboptimal systemic exposure.
OBJECTIVES: To assess whether the neurological or gastrointestinal adverse effects of ritonavir correlate with parameters of ritonavir systemic exposure. METHODS: Peak (Cmax) and trough (Cmin) ritonavir plasma levels were compared in 11 patients experiencing side-effects (group A) versus 10 patients without side-effects (group B). Ritonavir was administered with the following escalation dosing scheme: 300, 400, 500 mg twice a day for 3, 4, and 5 days, respectively, then the full dose of 600 mg twice a day. Blood sampling was done in group A within 24 h of the occurrence of side-effects and in group B after at least 3 days of the full dosage regimen. RESULTS: Both Cmax and Cmax were significantly higher (Mann-Whitney U test) in patients with side-effects. Cmax was [median (interquartile range)] 26.7 (22.7-33.3) mg/l versus 16.2 (13.4-17.0) mg/l (P = 0.001) and Cmin was 12.6 (9.1-13.9) versus 7.5 (4.9-8.6) mg/l (P = 0.002). CONCLUSION:Patients with higher ritonavir concentrations are at a higher risk of experiencing neurological or gastrointestinal side-effects. Individualization of the dosage regimen, e.g. a downward titration of the ritonavir dose in patients with side-effects, guided by plasma level monitoring, may result in a substantial increase in the percentage of patients tolerating ritonavir without increasing the risk of treatment failure as a result of suboptimal systemic exposure.
Authors: Anjaiah Srirangam; Monica Milani; Ranjana Mitra; Zhijun Guo; Mariangellys Rodriguez; Hitesh Kathuria; Seiji Fukuda; Anthony Rizzardi; Stephen Schmechel; David G Skalnik; Louis M Pelus; David A Potter Journal: J Thorac Oncol Date: 2011-04 Impact factor: 15.609
Authors: Ighovwerha Ofotokun; Lumine H Na; Raphael J Landovitz; Heather J Ribaudo; Grace A McComsey; Catherine Godfrey; Francesca Aweeka; Susan E Cohn; Manish Sagar; Daniel R Kuritzkes; Todd T Brown; Kristine B Patterson; Michael F Para; Randi Y Leavitt; Angelina Villasis-Keever; Bryan P Baugh; Jeffrey L Lennox; Judith S Currier Journal: Clin Infect Dis Date: 2015-03-12 Impact factor: 9.079
Authors: Antonio Valentin; Matthew Morrow; Richard H Poirier; Karen Aleman; Richard Little; Robert Yarchoan; George N Pavlakis Journal: AIDS Res Hum Retroviruses Date: 2010-01 Impact factor: 2.205