China
Africa
Explore chapters and articles related to this topic
Ritonavir and Cobicistat
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
One of the classes of direct-acting antivirals utilized to treat hepatitis C are drugs inhibiting the NS3/4A protease enzyme. Paritaprevir is one of these agents and is included in an AbbVie combination therapy used for hepatitis C genotype 1. Paritaprevir is a CYP3A4 substrate; ritonavir is used to increase peak and trough concentrations and the AUC. Studies demonstrated an increased half-life of paritaprevir from ~ 3 to 5–8 hours and the AUC by 48-fold when a 300mg dose was given with 100 mg ritonavir (Menon et al., 2009). A phase IIa study comparing paritaprevir 250 mg and 150 mg daily, both with ritonavir 100 mg daily (plus ribavirin and ombitasvir) for 12 weeks demonstrated similar rates of sustained virological response (95% and 93%, respectively), suggesting the 150-mg dose be further investigated (Poordad et al., 2013). The approved combination tablet contains ritonavir 50 mg and paritaprevir 75 mg (as well as ombitasvir 12.5 mg), given as two tablets daily (total daily dose of 100 mg/150 mg/25 mg).
Elbasvir/grazoprevir treatment in an HCV-infected peritoneal dialysis patient
Published in Renal Failure, 2020
Jin Chen, Yi Li, Guisen Li, Lei Pu
There are very few reports on DAA regimens in PD patients. Aggarwal et al. treated HCV-infected dialysis patients with 15 sofosbuvir/velpatasvir courses, one PD patient enrolled. Treatment was generally safe and well tolerated. Patient achieved SVR12 after the therapy [14]. Borgia SM et al. used same regimen for dialysis patients, five PD patients included, minor adverse effects were observed in their patients, resulting in a cure rate of 95% [15]. The safety and efficacy of 12-week ombitasvir/paritaprevir/ritonavir treatment in PD patients were evaluated by Shuster et al. and Stark et al. Intensive pharmacokinetic data showed the individual concentration–time profiles for the drugs overlapped among patients, with considerable inter-patient variability. PD had minimal effects on drugs exposure (area under the curve, AUCs). All of their three PD patients completed treatment and achieved SVR12 [16,17]. Londoño et al. described Ombitasvir/paritaprevir/ritonavir and dasabuvir or Ombitasvir/paritaprevir/ritonavir with or without ribavirin (RBV) regimens in CKD patients, included twelve PD patients, no statistically significant differences were found across renal stages. Although anemia, asthenia and pruritus were the most common adverse events during treatment, regimens were also well tolerated in these patients. High SVR12 rate obtained (92.6%) is particularly noteworthy [18]. The above-mentioned reports indicated high cure rates and favorable safety profiles for the drugs in PD patients.
The pharmacological interactions between direct-acting antivirals for the treatment of chronic hepatitis c and psychotropic drugs
Published in Expert Review of Clinical Pharmacology, 2018
Carlos Roncero, Jose Luis Villegas, Maria Martínez-Rebollar, Maria Buti
This combination regimen shows many interactions with other concomitant drugs mainly due to the fact that ritonavir is a strong inhibitor of CYP3A and therefore, coadministration with any substance metabolized through CYP3A that is associated with serious adverse reactions is contraindicated. Ritonavir is also a BCRP, OATP2B1-transporter and P-gp inhibitor. Besides, paritaprevir is an inhibitor of the transporters OATP1B1, OATP1B3, and OATP2B1, a BCRP and a UGT1A1 inhibitor, being able to increase the concentration of these transporters substrates. Finally, ombitasvir is a UGT1A1 inhibitor. On the other hand, CYP3A, P-gp, BCRP, and OATP1B1/OATP1B3 transporters inhibitors may increase the concentration of paritaprevir. And CYP3A4 inducers may decrease the concentration of ombitasvir, paritaprevir, and ritonavir, reducing their therapeutic effect.
Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV)
Published in Expert Review of Anti-infective Therapy, 2022
Sandra Abdul Massih, Ahizechukwu C. Eke
During pregnancy, increase in plasma concentration of progesterone is usually associated with longer gastric emptying times, increased gastric pH, and longer times to achieve Tmax [52,53]. The prolonged gastrointestinal emptying times during pregnancy can affect the concentration of drugs whose absorption are influenced by food, like Ombitasvir/Paritaprevir/Ritonavir/Dasbuvir (OBV/PTV/r/DSV), and SIM [36]. The increased gastric pH due to lower acid and higher mucus production affects ionization and absorption of acidic HCV drugs, leading to reduced absorption [52,54]. For instance, LDV is a weak acid, and has the potential for decreased absorption during pregnancy due to complexities with drug ionization at the gastrointestinal interphase.