scholarly journals Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thomas Kakuda ◽  
Vanitha Sekar ◽  
Peter Vis ◽  
Bruce Coate ◽  
Robert Ryan ◽  
...  
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Clinical Experience ◽  
Response Rates ◽  
Virologic Response ◽  
Time Dependent ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Lower Response ◽  
Dependent Relationship ◽  
Hiv 1

Objectives. Evaluation of pharmacokinetics and pharmacodynamics of darunavir and etravirine among HIV-1–infected, treatment-experienced adults from GRACE, by sex and race.Methods. Patients received darunavir/ritonavir 600/100mg twice daily plus other antiretrovirals, which could include etravirine 200mg twice daily. Population pharmacokinetics for darunavir and etravirine were determined over 48 weeks and relationships assessed with virologic response and safety. Rich sampling for darunavir, etravirine, and ritonavir was collected in a substudy at weeks 4, 24, and 48.Results. Pharmacokinetics were estimated in 376 patients for darunavir and 190 patients for etravirine. Median darunavir and were 60,642ng·h/mL and 3624ng/mL, respectively; and for etravirine were 4183ng · h/mL and 280ng/mL, respectively. There were no differences in darunavir or etravirine or by sex or race. Age, body weight, or use of etravirine did not affect darunavir exposure. No relationships were seen between darunavir pharmacokinetics and efficacy or safety. Patients with etravirine exposure in the lowest quartile generally had lower response rates. Rich sampling showed no time-dependent relationship for darunavir, etravirine, or ritonavir exposure over 48 weeks.Conclusions. Population pharmacokinetics showed no relevant differences in darunavir or etravirine exposure by assessed covariates. Lower etravirine exposures were associated with lower response rates.

scholarly journals Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial

2018 ◽  
Vol 105 (3) ◽  
pp. 692-702 ◽  
Author(s):  
Sulggi A. Lee ◽  
Julian H. Elliott ◽  
James McMahon ◽  
Wendy Hartogenesis ◽  
Namandje N. Bumpus ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Population Pharmacokinetics And Pharmacodynamics ◽  
Latent Hiv ◽  
Hiv 1

Population Pharmacokinetics and Pharmacodynamics of Doripenem in Obese, Hospitalized Patients

2016 ◽  
Vol 51 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Eun Kyoung Chung ◽  
Megan R. Fleming ◽  
S. Christian Cheatham ◽  
Michael B. Kays
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Obese Patients ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Time Data ◽  
Population Pharmacokinetics And Pharmacodynamics ◽  
Drug Concentrations ◽  
Dosing Regimens

Background: Doripenem population pharmacokinetics and dosing recommendations are limited in obesity. Objective: To evaluate the population pharmacokinetics and pharmacodynamics of doripenem in obese patients. Methods: Hospitalized adults with a body mass index (BMI) ≥ 40 kg/m2 or total body weight (TBW) ≥45.5 kg over their ideal body weight received doripenem 500 mg every 8 hours, infused over 1 hour. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed for 5 intermittent and prolonged infusion dosing regimens to calculate probability of target attainment (PTA) at 40% and 100% fT>MIC (free drug concentrations above the minimum inhibitory concentration). Results: A total of 20 patients were studied: 10 in an intensive care unit (ICU) and 10 in a non-ICU. A 2-compartment model with first-order elimination best described the serum concentration-time data. Doripenem clearance (CL) was significantly associated with creatinine CL (CRCL), volume of the central compartment with TBW and ICU residence, and volume of the peripheral compartment with TBW ( P < 0.05). Using 40% fT>MIC, PTA was >90% for all simulated dosing regimens at MICs ≤2 mg/L. Using 100% fT>MIC, prolonged infusions of 1 g every 6 hours and 2 g every 8 hours achieved >90% PTA at MICs ≤2 mg/L. Conclusions: CRCL, ICU residence, and TBW are significantly associated with doripenem pharmacokinetics. Currently approved dosing regimens provide adequate pharmacodynamic exposures at 40% fT>MIC for susceptible bacteria in obese patients. However, prolonged infusions of larger doses are needed if a higher pharmacodynamic target is desired.

Population Pharmacokinetics and Pharmacodynamics of Nelfinavir and Its Active Metabolite M8 in HIV-1-Infected Children

2006 ◽  
Vol 25 (6) ◽  
pp. 538-543 ◽  
Author(s):  
Kristel M. L. Crommentuyn ◽  
Henri??tte J. Scherpbier ◽  
Taco W. Kuijpers ◽  
Ron A. A. Math??t ◽  
Alwin D. R. Huitema ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Active Metabolite ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Population Pharmacokinetics And Pharmacodynamics ◽  
Hiv 1

Sex and Gender Differences in Rilpivirine based ART - Data from the HIVCENTER Frankfurt

2019 ◽  
Vol 17 (5) ◽  
pp. 368-374
Author(s):  
G. Schüttfort ◽  
K. Philipp ◽  
P. de Leuw ◽  
E. Herrmann ◽  
G. Kann ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Virologic Failure ◽  
Response Rates ◽  
Virologic Response ◽  
Close Monitoring ◽  
Sex And Gender ◽  
Overall Response ◽  
Number Of Patients ◽  
And Gender ◽  
Gender Specific

Objectives: While Rilpivirine has shown high overall response rates in treatment-naïve patients without sex and gender specific differences in clinical trials, Sex and gender specific data in treatment experienced patients receiving rilpivirine are still limited. We conducted a 48 week efficacy and safety analysis in naïve and treatment experienced men and women using retrospective data from the HIVCENTER Frankfurt. Materials and methods: In this retrospective observational study data of all patients who received a rilpivirine based regimen at the HIVCENTER between March 2011 and December 2015 were analyzed. Primary endpoint was the proportion of patients with any discontinuation until week 48. Virologic response rates (FDA snapshot analysis; HIV-1 RNA <50 copies/mL) were assessed at week 48. Results: 194 patients (34% female) were included in the analysis. 74% were treatment-experienced and 26% naïve, respectively. Discontinuations were observed in 31 (15.9%) patients. Regarding sex differences, the proportion of discontinuations was significantly higher in women than in men (24.2% vs. 11.7%; p=0.024; ODDS-Ratio = 2.41; CI 1.12 – 5.18). Virologic failure occurred in 8 PLWHIV (4.1%). Conclusions: While virologic overall response rates to rilpivirine based ART were high for both treatment-experienced and -naïve patients the proportion of discontinuations was significantly higher in women (24.2% vs. 11.7%; p = 0.024; ODDS-Ratio = 2.41; CI 1.12 – 5.18). Although the total number of patients with virologic failure was low (4.1%), the higher rate of ART discontinuations in female patients receiving RPV require close monitoring in the first months of treatment addressing special needs of women living with HIV.

scholarly journals Incidence and Impact of Persistent Viremia on SVR Rates in Patients Receiving Direct-Acting Antiviral Therapy

2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Alicia B Carver ◽  
Autumn D Zuckerman ◽  
Joshua DeClercq ◽  
Leena Choi ◽  
Cody A Chastain
Keyword(s):  
Antiviral Therapy ◽  
Real World ◽  
Sustained Virologic Response ◽  
Response Rates ◽  
Virologic Response ◽  
Direct Acting Antiviral ◽  
Rapid Virologic Response ◽  
Persistent Viremia ◽  
Direct Acting ◽  
High Sustained Virologic Response

Abstract Rates of persistent viremia (PV) while on direct-acting antiviral therapy were low (5.7%) in a real-world cohort of 983 patients. High sustained virologic response rates were achieved both in patients with PV (92.9%) and those with rapid virologic response (96.5%), without significant differences.

Sign in / Sign up

Export Citation Format

Share Document