scholarly journals Pharmacokinetics of Saquinavir, Atazanavir, and Ritonavir in a Twice-Daily Boosted Double-Protease Inhibitor Regimen

2007 ◽  
Vol 51 (4) ◽  
pp. 1431-1439 ◽  
Author(s):  
Nils von Hentig ◽  
Axel Müller ◽  
Carsten Rottmann ◽  
Timo Wolf ◽  
Thomas Lutz ◽  
...  
Keyword(s):  
Steady State ◽  
Protease Inhibitor ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Life Time ◽  
Time Curve ◽  
Once Daily ◽  
Therapy Regimen ◽  
Drug Concentrations ◽  
Group 2

ABSTRACT The objective of this study was to evaluate the pharmacokinetics of atazanavir (ATV), saquinavir (SQV), and ritonavir (RTV) in a boosted double-protease inhibitor (PI) therapy regimen without reverse transcriptase inhibitors (RTIs). The study design was as follows. Patients with limited RTI options received a PI combination of 300/100 mg ATV/RTV once daily and 1,000 mg SQV twice daily (group 1; n = 49) without RTI comedication. The results were compared to the plasma concentrations of PIs of patients taking either 300 mg ATV/100 mg RTV once daily plus RTIs (group 2; n = 72) or patients taking 1,000 mg SQV/100 mg RTV plus RTIs (group 3; n = 90). The study methods were as follows. Patients were given a 12/24-h pharmacokinetic assessment at steady state. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. The minimum and maximum concentrations (C min and C max), area under the concentration-time curve under steady-state conditions (AUCss), elimination half-life, time of maximum concentration and lag time were subject to statistical analysis. The results show that patients treated with ATV/SQV/RTV exhibited significantly high SQV concentrations and moderate enhancement of the AUCss of ATV in comparison to those of patients of the control groups: for SQV in groups 1 and 3, the geometric mean (GM) of the AUCss was 22,794 versus 15,759 ng·h/ml (GM ratio [GMR] = 1.45; P < 0.05), the GM of the C max was 3,257 versus 2,331 ng/ml (GMR = 1.40; P < 0.05), and the GM of the C min was 438 versus 437 ng/ml (GMR = 1.00); for ATV in groups 1 and 2, the GM of the AUCss was 39,154 versus 33,626 ng·h/ml (GMR = 1.16), the GM of the C max was 3,488 versus 2,924 ng/ml (GMR = 1.20), and the GM of the C min was 515 versus 428 ng/ml (GMR = 1.21). RTV levels were comparable for all groups. A subgroup analysis detected only marginal differences in ATV plasma exposure if combined with tenofovir-disoproxilfumarate and without it. We conclude that our pharmacokinetic results support the use of a boosted double-PI regimen of ATV/SQV/RTV as a treatment option for patients who need antiretroviral therapy without RTIs.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Pharmacokinetic study of lenvatinib in Chinese patients with solid tumors

2021 ◽  
Author(s):  
Dan Liu ◽  
Lei Liu ◽  
Lin Shen ◽  
Tomoki Kubota ◽  
Takuya Suzuki ◽  
...  
Keyword(s):  
Steady State ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Chinese Patients ◽  
Pharmacokinetic Data ◽  
Maximum Plasma ◽  
Clinical Trial Registration ◽  
Time Curve ◽  
Once Daily ◽  
Appropriate Treatment

Aim: To assess the pharmacokinetics of once-daily oral lenvatinib 24 mg in Chinese patients. Material & methods: Patients had any solid tumor (except hepatocellular carcinoma) that was resistant to standard antitumor therapies or for which no appropriate treatment was available. Results: Twelve patients were enrolled. Maximum plasma concentrations of lenvatinib were observed at 2 and 4 h (median) after single and multiple doses (day 15), respectively. Steady state was achieved within 8 days. The geometric mean maximum observed concentration at steady state was 258 ng/ml (coefficient of variance: 49.2%); and the geometric mean area under the concentration-time curve from zero to 24 h at steady state was 3090 ng•h/ml (coefficient of variance: 44.7%). No accumulation was seen after 15 days. Conclusion: Lenvatinib pharmacokinetic data in Chinese patients are consistent with data in multinational trials, supporting usage of the 24-mg dose. Clinical Trial Registration: NCT03009292 (ClinicalTrials.gov)

scholarly journals Pharmacokinetics of Darunavir at 900 Milligrams and Ritonavir at 100 Milligrams Once Daily when Coadministered with Efavirenz at 600 Milligrams Once Daily in Healthy Volunteers

2010 ◽  
Vol 54 (7) ◽  
pp. 2775-2780 ◽  
Author(s):  
Gaik H. Soon ◽  
Ping Shen ◽  
Eu-Leong Yong ◽  
Paul Pham ◽  
Charles Flexner ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Half Life ◽  
Geometric Mean ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Time Curve ◽  
Once Daily ◽  
Drug Concentrations ◽  
Trough Concentrations

ABSTRACT Ritonavir-boosted darunavir with efavirenz may be considered a nucleoside-sparing regimen for treatment-naïve HIV-infected patients. However, the pharmacokinetics of this combination administered once daily have not been studied. We conducted a three-period interaction study with healthy volunteers. The subjects were given darunavir at 900 mg with ritonavir at 100 mg once daily for 10 days. Efavirenz at 600 mg once daily was added for 14 days. Darunavir-ritonavir was then stopped and efavirenz alone was given for 14 days. At the end of each period, blood was taken predosing and for up to 24 h postdosing to measure the drug concentrations. We recruited seven males and five females ages 24 to 49 years and weighing 50 to 83 kg. The darunavir trough concentrations were reduced after efavirenz administration (geometric mean ratio [GMR], 0.43; 90% confidence interval [CI], 0.32 to 0.57]; P < 0.001). The mean darunavir trough concentrations were 1,180 ng/ml (standard deviation, 1,138 ng/ml) after efavirenz administration, but all darunavir trough concentrations were above the 50% effective concentration (EC50) of 55 ng/ml for the wild-type virus. For darunavir, the area under the concentration-time curve from 0 to 24 h (AUC0-24) (GMR, 0.86; 90% CI, 0.75 to 0.97; P = 0.05) and the half-life (GMR, 0.56; 90% CI, 0.49 to 0.65; P < 0.001) were also significantly reduced. The darunavir peak concentrations were not significantly changed (GMR, 0.92; 90% CI, 0.82 to 1.03; P = 0.23). The ritonavir trough concentrations (GMR, 0.46; 90% CI, 0.33 to 0.63; P = 0.001), AUC0-24 (GMR, 0.74; 90% CI, 0.64 to 0.86; P = 0.004), and half-life (GMR, 0.80; 90% CI, 0.75 to 0.86; P < 0.001) were also significantly reduced. The efavirenz half-life was significantly longer when it was coadministered with darunavir-ritonavir than when it was given alone (GMR, 1.66; 90% CI, 1.24 to 2.23; P = 0.01), but there were no differences in the efavirenz trough or peak concentration or AUC0-24 when it was coadministered with darunavir-ritonavir. Efavirenz reduced the trough concentrations of darunavir significantly, but the concentrations remained above the EC50 for the wild-type virus. This regimen should be evaluated with treatment-naïve patients with no preexisting resistance.

scholarly journals Switch from Enfuvirtide to Raltegravir Lowers Plasma Concentrations of Darunavir and Tipranavir: a Pharmacokinetic Substudy of the EASIER-ANRS 138 Trial

2011 ◽  
Vol 55 (7) ◽  
pp. 3613-3615 ◽  
Author(s):  
Lauriane Goldwirt ◽  
Joséphine Braun ◽  
Nathalie de Castro ◽  
Isabelle Charreau ◽  
Aurélie Barrail-Tran ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Concentration Time ◽  
Background Regimen ◽  
Immunodeficiency Virus ◽  
Plasma Concentration Time Curve

ABSTRACTWe compared tipranavir and darunavir concentrations measured at steady state in 20 human immunodeficiency virus (HIV)-infected patients enrolled in the EASIER-ANRS 138 clinical trial who switched from enfuvirtide to raltegravir while maintaining the same background regimen. The geometric mean ratios of the observed predose concentration (Ctrough), maximum concentration of drug observed in plasma (Cmax), and area under the plasma concentration-time curve (AUC) before (day 0) and after (week 24) the switch were 0.49, 0.76, and 0.67 and 0.82, 0.68, and 0.64 for tipranavir and darunavir, respectively. The virologic consequences of these drug interactions have yet to be determined.

An Open, Phase I Study of Cediranib in Patients with Acute Myeloid Leukemia (AML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 895-895
Author(s):  
Walter Fiedler ◽  
Rolf Mesters ◽  
Michael Heuser ◽  
Gerhard Ehninger ◽  
Oliver G. Ottman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Dose Escalation ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Biologically Active ◽  
Minor Response ◽  
Once Daily ◽  
Oral Doses ◽  
Refractory Aml

Abstract Prognosis is poor for the majority of AML patients, particularly the elderly and those with relapsed or refractory AML, and more effective treatment options are needed. Vascular endothelial growth factor-A (VEGF) and its receptors (VEGFRs) may contribute to the pathophysiology of AML and are considered as potential therapeutic targets. Cediranib (RECENTIN™; AZD2171) is an oral, highly potent and selective VEGF signaling inhibitor with activity versus VEGFR-1, -2 and -3, and additional activity against c-Kit. This two-part study evaluated the safety and tolerability of multiple once-daily oral doses of cediranib in patients with relapsed or refractory AML and elderly patients with de novo or secondary AML, with secondary assessments of pharmacokinetics (PK), pharmacodynamics (PD) and efficacy. Part A was a dose-escalation phase to determine the maximum tolerated dose (MTD); Part B was an expansion phase to explore the MTD and a lower, biologically active dose. A total of 35 patients (mean age, 68 years [range 50–81]; 15 male, 20 female) entered the study and received treatment with cediranib (Part A, n=23; Part B, n=12). Part A comprised 10mg (n=4), 20mg (n=6) and 30mg (n=13) dose cohorts, and intra-patient dose escalation was permitted. In Part B, patients received cediranib 20mg (n=3) or 30mg (n=9). Cediranib ≤30mg was generally well tolerated; diarrhea (n=19), hypertension (n=14) and fatigue (n=13) were the most common adverse events (AEs). Cediranib 30mg was the highest dose studied, and was declared the MTD based on dose-limiting toxicities of hypertension and diarrhea experienced by 3 patients receiving 30mg in Part A. Maximal plasma concentrations at steady-state were attained 0.83–4.1 h post-dosing. Steady-state plasma concentrations were attained after approximately 7 days of repeated once-daily dosing. Following multiple oral doses of cediranib 30mg in Parts A and B, the unbound geometric mean Css,min was 5x the IC50 value required to inhibit proliferation of human umbilical vein endothelial cells in preclinical assays, supporting the once-daily oral dosing regimen. The relationship between PK and two PD parameters (VEGF levels and blood pressure) were investigated and there appeared to be a positive correlation between exposure (Css,max and AUCss) and plasma VEGF levels, but not blood pressure. Time-dependent changes in soluble VEGFR-2 levels were observed. A best investigator assessment of AML objective response according to predefined criteria (Cheson et al, J Clin Oncol2003;21:4642–9) was observed for 6 patients (1 morphological complete remission with incomplete blood recovery [Cri], 4 partial responses and 1 minor response). However, none of the responses resulted in improvement in normal hemopoiesis. No responses were observed in 6 patients with Flt-3 ITD mutations. One patient remained on treatment for 455 days. Once-daily oral cediranib ≤30mg was generally well tolerated in patients with AML, with encouraging preliminary evidence of activity as a monotherapy. The AE and PK profiles of cediranib in AML are consistent with those seen in solid tumors.

scholarly journals Pharmacokinetics and Pharmacogenomics of Once-Daily Raltegravir and Atazanavir in Healthy Volunteers

2010 ◽  
Vol 54 (11) ◽  
pp. 4619-4625 ◽  
Author(s):  
Michael Neely ◽  
Laurent Decosterd ◽  
Aurélie Fayet ◽  
Janice Soo Fern Lee ◽  
Ashley Margol ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Volunteers ◽  
Geometric Mean ◽  
Metabolite Formation ◽  
Time Curve ◽  
Once Daily ◽  
Liquid Chromatography Tandem Mass ◽  
Urine Concentrations ◽  
Multiple Samples

ABSTRACT Atazanavir inhibits UDP-glucuronyl-transferase-1A1 (UGT1A1), which metabolizes raltegravir, but the magnitude of steady-state inhibition and role of the UGT1A1 genotype are unknown. Sufficient inhibition could lead to reduced-dose and -cost raltegravir regimens. Nineteen healthy volunteers, age 24 to 51 years, took raltegravir 400 mg twice daily (arm A) and 400 mg plus atazanavir 400 mg once daily (arm B), separated by ≥3 days, in a crossover design. After 1 week on each regimen, raltegravir and raltegravir-glucuronide plasma and urine concentrations were measured by liquid chromatography-tandem mass spectrometry in multiple samples obtained over 12 h (arm A) or 24 h (arm B) and analyzed by noncompartmental methods. UGT1A1 promoter variants were detected with a commercially available kit and published primers. The primary outcome was the ratio of plasma raltegravir C tau, or concentration at the end of the dosing interval, for arm B (24 h) versus arm A (12 h). The arm B-to-arm A geometric mean ratios (95% confidence interval, P value) for plasma raltegravir C tau, area under the concentration-time curve from 0 to 12 h (AUC0-12), and raltegravir-glucuronide/raltegravir AUC0-12 were 0.38 (0.22 to 0.65, 0.001), 1.32 (0.62 to 2.81, 0.45), and 0.47 (0.38 to 0.59, <0.001), respectively. Nine volunteers were heterozygous and one was homozygous for a UGT1A1 reduction-of-function allele, but these were not associated with metabolite formation. Although atazanavir significantly reduced the formation of the glucuronide metabolite, its steady-state boosting of plasma raltegravir did not render the C tau with a once-daily raltegravir dose of 400 mg similar to the C tau with the standard twice-daily dose. UGT1A1 promoter variants did not significantly influence this interaction.

scholarly journals Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

2014 ◽  
Vol 59 (1) ◽  
pp. 498-504 ◽  
Author(s):  
David Joseph ◽  
Michael J. Schobelock ◽  
Robert R. Riesenberg ◽  
Bradley D. Vince ◽  
Lynn R. Webster ◽  
...  
Keyword(s):  
Steady State ◽  
Maximum Dose ◽  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
State Concentration ◽  
State Area

ABSTRACTThe effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered atClinicalTrials.govunder registration no. NCT01637922.)

Ritonavir-Enhanced Pharmacokinetics of Nelfinavir/M8 during Rifampin Use

2003 ◽  
Vol 37 (4) ◽  
pp. 521-525 ◽  
Author(s):  
Alina S Bergshoeff ◽  
Tom FW Wolfs ◽  
Sibyl PM Geelen ◽  
David M Burger
Keyword(s):  
Steady State ◽  
Protease Inhibitor ◽  
Highly Active Antiretroviral Therapy ◽  
Adult Population ◽  
Plasma Concentrations ◽  
Pharmacokinetic Interaction ◽  
Male Infant ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Highly Active

OBJECTIVE: To describe a case of successful protease inhibitor–based highly active antiretroviral therapy (HAART) concomitant with rifampin. CASE SUMMARY: In a 7-month-old male infant with tuberculosis and HIV-1 infection, tuberculosis therapy including rifampin and HAART containing the protease inhibitor nelfinavir 40 mg/kg every 8 hours was started. Intensive steady-state pharmacokinetic sampling from baseline to 8 hours revealed very low plasma concentrations of nelfinavir: area under the plasma concentration–time curve (AUC0–24) <10% of adult population values for 750 mg every 8 hours and nonquantifiable concentrations of nelfinavir's principal metabolite (M8). Nelfinavir 40 mg/kg every 8 hours was then substituted with nelfinavir 30 mg/kg twice daily plus ritonavir 400 mg/m2 twice daily. Intensive steady-state (0–12 h) pharmacokinetic sampling was repeated. Nelfinavir concentrations had improved, but remained low when compared with adult population values of 1250 mg every 12 hours: AUC0–24 21.9 versus 47.6 mg/L•h (46%) and 12-hour trough level (C12) 0.25 versus 0.85 mg/L (29%). However, concentrations of M8 considerably exceeded population values: AUC0–24 57.5 versus 13.6 mg/L•h (443%) and C12 1.35 versus 0.28 mg/L (482%). Since M8 concentrations were highly elevated, pharmacokinetic parameters for (nelfinavir + M8) were used rather than those for nelfinavir alone. Thus, AUC0–24 (nelfinavir + M8) and C12 (nelfinavir + M8) comprised 130% and 142%, respectively of the adult population values. This, in addition to good clinical response and tolerability, favored continuation of the regimen. CONCLUSIONS: In an infant, nelfinavir-containing HAART was successfully used with rifampin after the addition of ritonavir. Ritonavir resolved the pharmacokinetic interaction between rifampin and nelfinavir by boosting nelfinavir and, especially, M8 concentrations. More research is needed to confirm these results.

scholarly journals Drug Interactions Between Dolutegravir and Artemether-Lumefantrine or Artesunate-Amodiaquine

2018 ◽  
Author(s):  
Stephen I Walimbwa ◽  
Mohammed Lamorde ◽  
Catriona Waitt ◽  
Julian Kaboggoza ◽  
Laura Else ◽  
...  
Keyword(s):  
Maximum Concentration ◽  
Geometric Mean ◽  
Compartmental Analysis ◽  
Sub Saharan Africa ◽  
Pharmacokinetic Studies ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Once Daily ◽  
Trough Concentrations ◽  
Sub Saharan

ABSTRACTAcross sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artmether-lumefantrine (AL) or artesunate-amodiaquine (AS-AQ) given with 50mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artmether-lumefantrine or artesunate-amodiaquine and DTG. The DTG/artmether-lumefantrine interaction was evaluated in a two-way cross-over study and measured artemether (ARM), dihydroartemisinin (DHA), lumefantrine (LF), desbutyl-lumefantrine (DBL) over 264h. The DTG/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine (DEAQ) and measured artesunate (ARS), amodiaquine (AQ), DEAQ over 624h. Non-compartmental analysis was performed, and geometric mean ratios and 90% confidence intervals generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, time to maximum concentration and area under the concentration-time curve (AUC) for ARM, DHA, LF and DBL nor significantly alter AUC for ARS, DHA, AQ and DEAQ. Co-administration of dolutegravir with AL resulted in a 37% decrease in DTG trough concentrations. Co-administration of dolutegravir with AS-AQ resulted in a decrease of approximately 42% and 24% in DTG trough concentrations and AUC respectively. Study drugs were well-tolerated with no serious adverse events. Standard doses of artmether-lumefantrine and artesunate-amodiaquine should be used in patients receiving DTG. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and DTG exposure with artesunate-amodiaquine are unlikely to be of clinical significance as DTG trough concentrations were above DTG target concentrations of 64ng/mL.

scholarly journals Fosamprenavir plus Ritonavir Increases Plasma Ketoconazole and Ritonavir Exposure, while Amprenavir Exposure Remains Unchanged

2007 ◽  
Vol 51 (8) ◽  
pp. 2982-2984 ◽  
Author(s):  
Mary B. Wire ◽  
Charles H. Ballow ◽  
Julie Borland ◽  
Mark J. Shelton ◽  
Yu Lou ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Subjects ◽  
Open Label ◽  
Time Curve ◽  
Once Daily ◽  
Open Label Study ◽  
Label Study ◽  
Concentration Time

ABSTRACT Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV) pharmacokinetics were evaluated in 15 healthy subjects after being treated with KETO at 200 mg once daily (QD), fosamprenavir (FPV)/RTV at 700/100 mg twice daily (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open-label study. The KETO area under the concentration-time curve at steady state was increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure was slightly increased.

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