Steady‐state pharmacokinetic interaction of modified‐dose indinavir and rifabutin

Hamzeh, Fayez M.

doi:10.1067/mcp.2003.3

Cited by 36 publications

(39 citation statements)

References 29 publications

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“…A rash occurs more frequently with a higher withdrawal rate in healthy subjects receiving FPV-RTV (7)(8)(9) than in HIV-infected patients receiving FPV-RTV (Lexiva [fosamprenavir calcium] product information, June 2006), which may in part reflect a different risk-benefit profile for patients and a true potential for less-frequent rashes in HIVinfected patients. Safety findings were also similar to those in other studies of protease inhibitors coadministered with RFB (2,3,5). Therefore, the coadministration of RFB and FPV-RTV does not appear to cause safety concerns in addition to those of either treatment alone.…”

Section: Discussionsupporting

confidence: 76%

“…The combination of RFB (150 mg QOD) and FPV-RTV (700/100 mg BID) for 14 days had a side effect profile similar to previously described events with RFB or FPV-RTV alone (1,2). Neutropenia (absolute neutrophil count of Ͻ750/mm 3 ) has been found in 25% of subjects receiving RFB in efficacy studies (Mycobutin product information, February 2002) but has not been reported for healthy subjects receiving FPV with or without RTV (4,(6)(7)(8)(9).…”

Section: Discussionmentioning

confidence: 89%

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Pharmacokinetic Interaction between Fosamprenavir-Ritonavir and Rifabutin in Healthy Subjects

Ford

Chen

Lou

et al. 2008

Antimicrob Agents Chemother

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Rifabutin (RFB) is administered for treatment of tuberculosis and Mycobacterium avium complex infection, including use for patients coinfected with human immunodeficiency virus (HIV).Plasma exposure to RFB and dAc-RFB, both substrates of CYP3A4, has been increased significantly by coadministration with CYP3A4 inhibitors, including HIV protease inhibitors (PIs) (1, 5), which has the potential to increase the risk of RFB-associated adverse events, including neutropenia and uveitis (Mycobutin product information, February 2002). Concomitant administration of amprenavir (APV) (1,200 mg twice a day [BID]) and RFB (300 mg once per day [QD]) for 10 days increased plasma RFB AUC from 0 to 24 h (AUC 0-24 ) and maximum concentration (C max ) 2.9-and 2.2-fold, respectively, and increased plasma dAc-RFB AUC 0-24 , C max , and minimum concentration 13.3-, 7.4-, and 32.9-fold, respectively, relative to those of RFB (300 mg once a day [QD]) alone; a 50% reduction in the RFB dose was recommended for the combination of RFB and unboosted APV (5). Similarly, coadministration of lopinavir (LPV)-ritonavir (RTV) (400/100 mg BID) and a 50%-reduced RFB dose (150 mg QD) for 10 days increased plasma RFB AUC 0-24 and C max 3.0-and 4.9-fold, respectively, increased the plasma dAc-RFB AUC 0-24 , C max , and minimum concentration 47.5-, 23.6-and 94.9-fold, respectively, and increased the total antimycobacterial AUC 0-24 5.7-fold relative to those of RFB (300 mg QD) alone (Kaletra [lopinavir-ritonavir] product information, January 2006). A reduction in the RFB dosage of at least 75% is recommended during coadministration with LPV-RTV (Kaletra product information, January 2006). Also an inducer of CYP3A4, RFB (300 mg QD) has been associated with a 34% reduction in indinavir AUC (3) and a 15% reduction in APV AUC (5), which increases the risk to patients for subtherapeutic antiretroviral treatment; however, LPV AUC was unchanged following administration of LPV-RTV (400/100 mg BID) with RFB (150 mg QD) (Kaletra product information, January 2006). Fosamprenavir (FPV) (Lexiva or Telzir), the phosphate ester prodrug of the HIV type 1 PI APV, is approved for the treatment of HIV infection in adults and can be administered with or without RTV (Lexiva [fosamprenavir calcium] product

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 89%

Pharmacokinetic Interaction between Fosamprenavir-Ritonavir and Rifabutin in Healthy Subjects

Ford

Chen

Lou

et al. 2008

Antimicrob Agents Chemother

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“…The addition of HIV protease inhibitors, such as ritonavir, atazanavir, indinavir, and saquinavir, all of which are known to be P-gp inhibitors, at 10 M (a concentration in the range or above clinically relevant plasma concentrations) (Hamzeh et al, 2003;Cook et al, 2004;McCance-Katz et al, 2007), did not significantly (p Ͼ 0.05) reduce the efflux. The strongest inhibition within this class of compounds was observed for ritonavir.…”

Section: Resultsmentioning

confidence: 98%

In Vitro and In Vivo P-Glycoprotein Transport Characteristics of Rivaroxaban

Gnoth

Buetehorn²,

Muenster³

et al. 2011

J Pharmacol Exp Ther

194

151

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Rivaroxaban, an oral, direct factor Xa inhibitor, has a dual mode of elimination in humans, with two-thirds metabolized by the liver and one-third renally excreted unchanged. P-glycoprotein (P-gp) is known to be involved in the absorption, distribution, and excretion of drugs. To investigate whether rivaroxaban is a substrate of P-gp, the bidirectional flux of rivaroxaban across Caco-2, wild-type, and P-gp-overexpressing LLC-PK1 cells was investigated. Furthermore, the inhibitory effect of rivaroxaban toward P-gp was determined. Rivaroxaban exhibited high permeability and polarized transport across Caco-2 cells. Rivaroxaban was shown to be a substrate for, but not an inhibitor of, P-gp. Of a set of potential P-gp inhibitors, ketoconazole and ritonavir, but not clarithromycin or erythromycin, inhibited Pgp-mediated transport of rivaroxaban, with half-maximal inhibitory concentration values in the range of therapeutic plasma concentrations. These findings are in line with observed area under the plasma concentration-time curve increases in clinical drug-drug interaction studies indicating a possible involvement of P-gp in the distribution and excretion of rivaroxaban. In vivo studies in wild-type and P-gp double-knockout mice demonstrated that the impact of P-gp alone on the pharmacokinetics of rivaroxaban is minor. However, in P-gp double-knockout mice, a slight increase in brain concentrations and decreased excretion into the gastrointestinal tract were observed compared with wild-type mice. These studies also demonstrated that brain penetration of rivaroxaban is fairly low. In addition to P-gp, a further transport protein might be involved in the secretion of rivaroxaban.

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“…(Kashuba, 2005) Combined administration of antacids does not seem to significantly affect the amount absorbed of fosamprenavir, (Ford et al, 2005) or raltegravir; however it is recommended to separate the taking of the two drugs when they are used in pharmacological therapy. (Kiser et al, 2010) Aaron et al, 2004;Benator et al, 2007;Blumberg et al, 2003;DeJong et al 2004;Finch et al, 2002;Hamzeh et al, 2003;Kraft et al, 2004;La Porte et al, 2004;Polk et al, 2001;Ribera et al, 2007;Rolla et al, 2006;Spradling et al, 2002) Ritonavir (Aaron et al, 2004;Blumberg et al, 2003;DeJong et al 2004;Finch et al, 2002;Spradling et al, 2002) 1: very high risk 2: high risk Adjust rifabutin dose 150 mg/48 hours, with no change in ritonavir Indinavir (Hamzeh et al, 2003, Kraft et al, 2004 1: very high risk 2: high risk Adjust the dose of rifabutin 150 mg/24 hours and indinavir at 1,000 mg/8 hours Saquinavir (Aaron et al, 2004;Blumberg et al, 2003;DeJong et al 2004;Finch et al, 2002;Ribera et al, 2007;Rolla et al, 2006;Spradling et al, 2002) 1: very high risk 2: high risk Use usual dose of rifabutin (300 mg/day), with no change in saquinavir Nelfinavir (Aaron et al, 2004;Benator et al, 2007;Blumberg et al, 2003;DeJong et al 2004;…”

Section: Drug Interactions Related To Bioavailability 351 Drug Intementioning

confidence: 99%

“…This combination is considered absolutely contraindicated McCance-Katz et al, 2006;Matteelli et al, 2007a;Ramachandran et al, 2006;Ribera et al, 2001) Delavirdine (Borin et al, 1997;DeJong et al 2004;McCance-Katz et al, 2006;Spradling et al, 2002) Nevirapine (Benator et al, 2007;Blumberg et al, 2003;Borin et al, 1997;Burger et al, 2006;Hamzeh et al, 2003;Kraft et al, 2004;La Porte et al, 2004;Polk et al, 2001;Ramachandran et al, 2006;Ribera et al, 2001Ribera et al, , 2007Rolla et al, 2006) 2: high risk 3: medium risk…”

Section: : Very High Riskmentioning

confidence: 99%

Clinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy

Amariles¹,

Alzate²,

Faus³

2011

Understanding HIV/AIDS Management and Care - Pandemic Approaches in the 21st Century

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Steady‐state pharmacokinetic interaction of modified‐dose indinavir and rifabutin

Cited by 36 publications

References 29 publications

Pharmacokinetic Interaction between Fosamprenavir-Ritonavir and Rifabutin in Healthy Subjects

Pharmacokinetic Interaction between Fosamprenavir-Ritonavir and Rifabutin in Healthy Subjects

In Vitro and In Vivo P-Glycoprotein Transport Characteristics of Rivaroxaban

Clinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy

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