Abstract 527: Vorapaxar Does Not Increase Bleeding Time

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Walter Kraft ◽  
Jocelyn Gilmartin ◽  
Derek L Chappell ◽  
Srikanth Nagalla ◽  
Uhlas P Naik ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Clinical Trial Data ◽  
Open Label ◽  
Period 2 ◽  
Parallel Group ◽  
The Us ◽  
Surgical Bleeding ◽  
Group 2

Vorapaxar is a novel PAR-1 inhibitor approved in the US and EU to reduce risk of thrombotic CV events in patients with a history of MI, and in the US also in patients with PAD. It does not affect coagulation tests (TT, PT, aPTT, ACT, ECT). Aspirin and P2Y 12 inhibitors prolong human bleeding time (BT); does vorapaxar? Methods: In this randomized, active controlled, parallel group, 2-period, single-blind, open-label trial, healthy men (n=31) and women (n=5), in Period 1, received either 81 mg aspirin (ASA) QD for 7 days (N=18), or a 7 day regimen of vorapaxar (N=18) achieving steady state plasma concentrations equivalent to chronic 2.5 mg QD doses. In Period 2, each group added 7 days of the therapy alternate to that of Period 1 without washout. BT and platelet aggregation (PA) using arachidonic acid, ADP, and TRAP agonists were collected predose in Periods 1 (baseline) and 2, and 24 h after Period 2 last dose. A linear mixed effects model with fixed effect for treatment analyzed data. Results: BT geometric mean ratio (90% CI) for (vorapaxar/baseline) was 1.01 (0.88, 1.15), (ASA/baseline) was 1.32 (1.15, 1.51), (vorapaxar+ASA/vorapaxar) was 1.47 (1.26, 1.70), (vorapaxar+ASA/ASA) was 1.12 (0.96, 1.30). Each antiplatelet inhibited PA only as expected. See figure. Conclusions: Unlike ASA, vorapaxar did not prolong BT compared to baseline. When given with ASA, there is a slight numerical increase in BT beyond that of ASA. Implications for clinical spontaneous or surgical bleeding await further analyses of clinical trial data.

scholarly journals Effect of Tipranavir-Ritonavir on Pharmacokinetics of Raltegravir

2009 ◽  
Vol 53 (7) ◽  
pp. 2752-2755 ◽  
Author(s):  
William D. Hanley ◽  
Larissa A. Wenning ◽  
Allison Moreau ◽  
James T. Kost ◽  
Eric Mangin ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Study Drug ◽  
Integrase Inhibitor ◽  
Phase Iii ◽  
Open Label ◽  
Time Curve ◽  
Period 2 ◽  
Adverse Experiences ◽  
Immunodeficiency Virus

ABSTRACT Raltegravir (RAL) is a novel and potent human immunodeficiency virus type 1 integrase inhibitor that is predominantly metabolized via glucuronidation. The protease inhibitor combination tipranavir (TPV) at 500 mg and ritonavir (RTV) at 200 mg (TPV-RTV) has inhibitory and inductive effects on metabolic enzymes, which includes the potential to induce glucuronosyltransferase. Because RAL may be coadministered with TPV-RTV, there is the potential for the induction of RAL metabolism. Consequently, we assessed the effect of TPV-RTV on the pharmacokinetics of RAL and the safety and tolerability of this combination. Eighteen healthy adults were enrolled in this open-label study. The participants received RAL at 400 mg twice daily for 4 days (period 1) and TPV-RTV twice daily for 7 days (period 2), followed immediately by 400 mg RAL with TPV-RTV twice daily for 4 days (period 3). Under steady-state conditions, the RAL concentration at 12 h (C 12) was decreased when RAL was administered with TPV-RTV (geometric mean ratio [GMR], 0.45; 90% confidence interval [CI] 0.31, 0.66; P = 0.0021); however, the area under the concentration-time curve from time zero to 12 h (GMR, 0.76; 90% CI, 0.49, 1.19; P = 0.2997) and the maximum concentration in serum (GMR, 0.82; 90% CI, 0.46, 1.46; P = 0.5506) were not substantially affected. There were no serious adverse experiences or discontinuations due to study drug-related adverse experiences, and RAL coadministered with TPV-RTV was generally well tolerated. Although the RAL C 12 was decreased with TPV-RTV in this study, favorable efficacy data collected in phase III studies substantiate that TPV-RTV may be coadministered with RAL without dose adjustment.

scholarly journals Lack of Effect of Efavirenz on the Pharmacokinetics of Tipranavir-Ritonavir in Healthy Volunteers

2009 ◽  
Vol 53 (11) ◽  
pp. 4840-4844 ◽  
Author(s):  
C. J. L. la Porte ◽  
J. P. Sabo ◽  
L. Béïque ◽  
D. W. Cameron
Keyword(s):  
Steady State ◽  
Multiple Dose ◽  
Healthy Adult ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Open Label ◽  
Multiple Dose Study ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Dose Study

ABSTRACT Previously it has been shown that tipranavir-ritonavir (TPV/r) does not affect efavirenz (EFV) plasma concentrations. This study investigates the effect of steady-state EFV on steady-state TPV/r pharmacokinetics. This was a single-center, open-label, multiple-dose study of healthy adult female and male volunteers. TPV/r 500/200 mg twice a day (BID) was given with food for 24 days. After dosing with TPV/r for 10 days, EFV 600 mg once a day was added to the regimen. Intensive pharmacokinetic (PK) sampling was done on days 10 and 24. Validated bioanalytical high-pressure liquid chromatography-tandem mass spectrometry methods were used to determine plasma tipranavir (TPV), ritonavir (RTV), and EFV concentrations. Thirty-four subjects were entered into the study, and 16 subjects completed it. The geometric mean ratios (90% confidence intervals) for TPV and RTV area under the curves, C maxs, and C mins comparing TPV/r alone and in combination with EFV were 0.97 (0.87 to 1.09), 0.92 (0.81 to 1.03), and 1.19 (0.93 to 1.54) for TPV and 1.03 (0.78 to 1.38), 0.92 (0.65 to 1.30), and 1.04 (0.72 to 1.48) for RTV. Frequently observed adverse events were diarrhea, headache, dizziness, abnormal dreams, and rash. EFV had no effect on the steady-state PK of TPV or RTV, with the exception of a 19% increase in the TPV C min, which is not clinically relevant. TPV/r can be safely coadministered with EFV and without the need for a dose adjustment.

scholarly journals Pharmacokinetics of Liposomal Amphotericin B for Injection in Chinese Healthy Subjects Based on a Bioequivalence Study

2021 ◽  
Author(s):  
Xueyuan Zhang ◽  
Huanhuan Qi ◽  
Manman Wang ◽  
Yuhuan Ji ◽  
Chunlei Li ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Bioequivalence Study ◽  
Liposomal Amphotericin B ◽  
Pharmacokinetic Parameters ◽  
Healthy Population ◽  
Open Label ◽  
Liposomal Form

Abstract Purpose: The aim of this study was to evaluate the pharmacokinetic characteristics and safety of Liposomal Amphotericin B for injection in healthy Chinese volunteers based on a pilot bioequivalence clinical trial between a generic formulation and Ambisome ® Methods: This randomized, two sequence, open label, single dose,two period crossover study was conducted in healthy volunteers at the dose of 2mg kg Blood samples were collected at pre defined time points up to 674 h after the start of the 2 h infusion. Plasma concentrations of total, unencapsulated and encapsulated amphotericin B were determined. Pharmacokinetic parameters were calculated using non compartmental model . The formulations were considered bioequivalent if the 90% confidence interval ls (CIs) of the geometric mean ratio of C max and AUC of both products for free and encapsulated amphotericin B were within80.00 1 25.00 for L n transformed data. Results and conclusion: All the 12subjects completed the two period study , no subjects withdrew the study. The plasma pharmacokinetic profile of liposomal amphotericin B based on free, encapsulated and total amphotericin B demonstrated the characteristics of a three compartment al model. The majority drug in the circulating system after IV infusion of liposomal amphotericin B is remained liposomal form . Pharmacokinetic behaviors in Chinese population w ere consistent with that in western healthy population based on total and unbound amphotericin B concentrations in plasma. The generic liposomal amphotericin B for injection is bioequivalent to Ambisome ® in terms of the Pharmacokinetic parameters for free, encapsulated and total amphotericin B. Trial registration number at National Medical Products Administration CTR20200885 . Date of registration: May 22 , 20 2 0.

An open-label, fixed-sequence study to evaluate the effect of encequidar (HM30181) an oral P-gp inhibitor, on the pharmacokinetics of dabigatran etexilate (a P-gp substrate) in healthy male volunteers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15060-e15060
Author(s):  
Christopher G. C. A. Jackson ◽  
Noelyn Anne Hung ◽  
David Cutler ◽  
Douglas Kramer ◽  
Jay Zhi ◽  
...  
Keyword(s):  
Treatment Period ◽  
Dabigatran Etexilate ◽  
Plasma Concentrations ◽  
Metastatic Breast ◽  
Healthy Male ◽  
Open Label ◽  
Fixed Sequence ◽  
Once Daily ◽  
Period 2 ◽  
Sequence Study

e15060 Background: Oral co-administration of encequidar (a selective, minimally absorbed oral P-gp inhibitor) 12.9 mg with paclitaxel (a P-gp substrate) 205 mg/m2 for 3 consecutive days per week can achieve comparable AUC exposure to that of IV paclitaxel 80mg/m2 with a significantly lowered Cmax and has been demonstrated its improved tumor response with reduced neuropathy compared to IV paclitaxel 175 mg/m2 Q3W for the treatment of patients with metastatic breast cancer. Because of its pharmacology as an inhibitor of P-gp, encequidar may increase the bioavailability of orally administered drugs that are substrates of P-gp, such as dabigatran etexilate. Methods: To determine the effect of a therapeutic dose and regimen (3 once-daily 12.9 mg doses) of encequidar on the single dose PK of dabigatran etexilate, an open-label, fixed-sequence study was performed in 20 healthy male subjects. Participants received a single oral dose of dabigatran etexilate 75 mg on Day 1 of Treatment Period 1 (reference) and, after a washout period of at least 7 days, on Days 3, 17 and 31 of Treatment Period 2, after receiving once-daily oral doses 12.9 mg encequidar on Days 1 to 3 of Period 2. The PK sampling for determination of plasma concentrations of total and unconjugated dabigatran lasted up to 48 hours postdose of each dabigatran etexilate dosr. Results: Mean AUC and Cmax values for dabigatran were both increased ̃ 95% without changing t½ when dabigatran etexilate was administered 1 hour post the 3rd dose of 12.9 mg encequidar compared to when dabigatran etexilate was administered alone. When dabigatran etexilate was administered 2 weeks after encequidar administration, no apparent differences in dabigatran AUC or Cmax were detected compared to those of dabigatran etexilate alone. When administered 4 weeks after discontinuation of encequidar, dabigatran AUC and Cmax were both slightly lower than Reference dabigatran etexilate (̃ 25% lower for AUC and 34% lower for Cmax). Both unconjugated and total dabigatran PK data were analyzed and shown to be similar. Encequidar and dabigatran etexilate were well tolerated and had acceptable safety findings in this healthy subject population. Conclusions: Concomitant dosing of encequidar with dabigatran etexilate resulted in < 2-fold increase in exposure to dabigatran, which had abated by the time of the first re-test, 14 days after the last dose of encequidar. The observed changes do not warrant dose adjustment of dabigatran etexilate when administered with encequidar. Clinical trial information: ACTRN12618000791235.

scholarly journals Pharmacokinetic Interaction between Maraviroc and Fosamprenavir-Ritonavir: an Open-Label, Fixed-Sequence Study in Healthy Subjects

2013 ◽  
Vol 57 (12) ◽  
pp. 6158-6164 ◽  
Author(s):  
Manoli Vourvahis ◽  
Anna Plotka ◽  
Laure Mendes da Costa ◽  
Annie Fang ◽  
Jayvant Heera
Keyword(s):  
Healthy Subjects ◽  
Geometric Mean ◽  
Active Form ◽  
Pharmacokinetic Interaction ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Open Label ◽  
Fixed Sequence ◽  
Dosing Interval ◽  
Period 2

ABSTRACTThis open-label, fixed-sequence, phase 1 study evaluated the pharmacokinetic interaction between maraviroc (MVC) and ritonavir-boosted fosamprenavir (FPV/r) in healthy subjects. In period 1, subjects received 300 mg of MVC twice daily (BID; cohort 1) or once daily (QD; cohort 2) for 5 days. In period 2, cohort 1 subjects received 700/100 mg of FPV/r BID alone on days 1 to 10 and then FPV/r at 700/100 mg BID plus MVC at 300 mg BID on days 11 to 20; cohort 2 subjects received FPV/r at 1,400/100 mg QD alone on days 1 to 10 and then FPV/r at 1,400/100 mg QD plus MVC at 300 mg QD on days 11 to 20. Pharmacokinetic parameters, assessed on day 5 of period 1 and on days 10 and 20 of period 2, included the maximum plasma concentration (Cmax), the concentration at end of dosing interval (Cτ), and the area under the curve over dosing interval (AUCτ). Safety and tolerability were also assessed. MVC geometric mean AUCτ,Cmax, andCτwere increased by 149, 52, and 374%, respectively, after BID dosing with FPV/r, and by 126, 45, and 80%, respectively, after QD dosing. Amprenavir (the active form of the prodrug fosamprenavir) and ritonavir exposures were decreased in the presence of MVC with amprenavir AUCτ,Cmax, andCτdecreased by 34 to 36% in the presence of FPV/r plus maraviroc BID and by 15 to 30% with FPV/r plus MVC QD both compared to FPV/r alone. The overall all-causality adverse-event (AE) incidence rate was 96.4%; all AEs were of mild or moderate severity. Commonly reported treatment-related AEs (>20% of patients overall) included diarrhea, fatigue, abdominal discomfort, headache, and nausea. No serious AEs or deaths occurred. In summary, maraviroc exposure increased in the presence of FPV/r, whereas MVC coadministration decreased amprenavir and ritonavir exposures. MVC dosed at 300 mg BID with FPV/r is not recommended due to concerns of lower amprenavir exposures; however, no dose adjustment is warranted with MVC at 150 mg BID in combination with FPV/r based on the available clinical data. MVC plus FPV/r was generally well tolerated; no new safety signals were detected.

scholarly journals Minimal Effects of Ritonavir and Efavirenz on the Pharmacokinetics of Raltegravir

2008 ◽  
Vol 52 (12) ◽  
pp. 4338-4343 ◽  
Author(s):  
Marian Iwamoto ◽  
Larissa A. Wenning ◽  
Amelia S. Petry ◽  
Martine Laethem ◽  
Marina De Smet ◽  
...  
Keyword(s):  
Maximum Concentration ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Strand Transfer ◽  
Time Curve ◽  
Period 2 ◽  
Immunodeficiency Virus ◽  
Transfer Inhibitor ◽  
Hiv 1

ABSTRACT Raltegravir is a novel human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor with potent in vitro activity against HIV-1 (95% inhibitory concentration = 31 nM in 50% human serum). The possible effects of ritonavir and efavirenz on raltegravir pharmacokinetics were separately examined. Two clinical studies of healthy subjects were conducted: for ritonavir plus raltegravir, period 1, 400 mg raltegravir; period 2, 100 mg ritonavir every 12 h for 16 days with 400 mg raltegravir on day 14; for efavirenz plus raltegravir, period 1, 400 mg raltegravir; period 2, 600 mg efavirenz once daily for 14 days with 400 mg raltegravir on day 12. In the presence of ritonavir, raltegravir pharmacokinetics were weakly affected: the plasma concentration at 12 h (C 12 h) geometric mean ratio (GMR) (90% confidence interval [CI]) was 0.99 (0.70, 1.40), area under the concentration-time curve from zero to infinity (AUC0 - ∞) was 0.84 (0.70, 1.01), and maximum concentration of drug in serum (C max) was 0.76 (0.55, 1.04). In the presence of efavirenz, raltegravir pharmacokinetics were moderately to weakly reduced: C 12 h GMR (90% CI) was 0.79 (0.49, 1.28); AUC0- ∞ was 0.64 (0.52, 0.80); and C max was 0.64 (0.41, 0.98). There were no substantial differences in the time to maximum concentration of drug in plasma or the half-life. Plasma concentrations of raltegravir were not substantially affected by ritonavir. Though plasma concentrations of raltegravir were moderately to weakly reduced by efavirenz, the degree of this reduction was not clinically meaningful. No dose adjustment is required for raltegravir with coadministration with ritonavir or efavirenz.

scholarly journals Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult Volunteers

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Amanda M. Healan ◽  
J. McLeod Griffiss ◽  
Howard M. Proskin ◽  
Mary Ann O'Riordan ◽  
Wesley A. Gray ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Adult ◽  
Controlled Trial ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Parameter Estimates ◽  
Open Label ◽  
Combination Drug ◽  
Period 2 ◽  
Adult Volunteers

ABSTRACT Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial ATP synthase. Bedaquiline has been used to effectively treat tuberculosis (TB) caused by drug-susceptible and drug-resistant Mycobacterium tuberculosis. Rifamycins are a cornerstone of combination drug regimens for the treatment of TB. This phase 1, open-label, randomized, controlled trial evaluated the effect of steady-state dosing of rifabutin or rifampin on the safety, tolerability, and pharmacokinetics of bedaquiline given as a single dose. Thirty-three healthy subjects were enrolled to receive a 400-mg single oral dose of bedaquiline at two time points, on study days 1 and 29. Subjects were randomly assigned to once daily oral doses of rifabutin (300 mg/day, n = 17) or rifampin (600 mg/day, n = 16) during period 2 from days 20 to 41. Serial blood sampling for bedaquiline measurement occurred on days 1 and 29 through 336 h after bedaquiline administration. The day 29 bedaquiline pharmacokinetic parameter estimates were compared to the corresponding day 1 estimates for each rifamycin group. Steady-state rifampin reduced bedaquiline AUC0–336 approximately 45%, from 47.69 h·μg/ml in period 1 to 26.33 h·μg/ml in period 2. Bedaquiline apparent clearance accelerated 24% in rifampin-treated subjects from 6.59 liters/h in period 1 to 8.19 liters/h in period 2. Steady-state rifabutin resulted in little quantitative impact on bedaquiline exposure but was associated with grade 3 and 4 adverse events before and after the day 29 bedaquiline dose. Dosage adjustments may therefore be necessary to ensure that bedaquiline plasma concentrations reach therapeutic levels safely when combining bedaquiline and rifamycins in TB treatment regimens. (This single-site, randomized, open-label, prospective study in healthy adult volunteers was registered at Clinicaltrials.gov under registration no. NCT01341184.)

scholarly journals Pharmacokinetic Characterisation and Comparison of Bioavailability of Intranasal Fentanyl, Transmucosal, and Intravenous Administration through a Three-Way Crossover Study in 24 Healthy Volunteers

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
S. Nardi-Hiebl ◽  
J. W. Ndieyira ◽  
Y. Al Enzi ◽  
W. Al Akkad ◽  
T. Koch ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Intravenous Administration ◽  
Intranasal Administration ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Published Data ◽  
Open Label ◽  
Single Dose Study ◽  
Transmucosal Administration

Background. For more than 60 years, the synthetic opioid fentanyl has been widely used in anaesthesia and analgesia. While the intravenous formulation is primarily used for general anaesthesia and intensive care settings, the drug’s high lipophilic properties also allow various noninvasive routes of administration. Published data suggest that intranasal administration is also attractive for use as intranasal patient-controlled analgesia (PCA). A newly developed intranasal fentanyl formulation containing 47 μg fentanyl, intravenous fentanyl, and oral transmucosal fentanyl citrate were characterised, and bioavailability was compared to assess the suitability of the intranasal formulation for an intranasal PCA product. Methods. 27 healthy volunteers were enrolled in a single-centre, open-label, randomised (order of treatments), single-dose study in a three-period crossover design. The pharmacokinetics of one intranasal puff of fentanyl formulation (47 μg, 140 mL per puff), one short intravenous infusion of 50 μg fentanyl, and one lozenge with an integrated applicator (200 μg fentanyl) were studied, and bioavailability was calculated. Blood samples were collected over 12 hours, and plasma concentrations of fentanyl were determined by HPLC with MS/MS detection. Results. 24 volunteers completed the study. The geometric mean of AUC0-tlast was the highest with oral transmucosal administration (1106 h  ∗  pg/ml, CV% = 32.86), followed by intravenous (672 h  ∗  pg/ml, CV% = 32.18) and intranasal administration (515 h  ∗  pg/ml, CV% = 30.10). Cmax was 886 pg/ml (CV% = 59.38) for intravenous, 338 pg/ml (CV% = 45.61) for intranasal, and 310 pg/ml (CV% = 29.58) for oral transmucosal administration. tmax was shortest for intravenous administration (0.06 h, SD = 0.056), followed by intranasal (0.21 h, SD = 0.078) and oral transmucosal administration (1.20 h, SD = 0.763). Dose-adjusted relative bioavailability was determined to be 74.70% for the intranasal formulation and 41.25% for the oral transmucosal product. In total, 38 adverse events (AEs) occurred. Fourteen AEs were potentially related to the investigational items. No serious AE occurred. Conclusion. Pharmacokinetic parameters and bioavailability of the investigated intranasal fentanyl indicated suitability for its intended use as an intranasal PCA option.

Abstract P100: Bioavailability of Arginine versus Erbumine Formulations of Perindopril in Healthy Subjects

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Andrew Bishop
Keyword(s):  
Adverse Event ◽  
Healthy Subjects ◽  
Mixed Model ◽  
Enzyme Inhibitor ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Mixed Model Analysis ◽  
Track Record ◽  
Period 2

Perindopril is an angiotensin converting-enzyme inhibitor with a proven track record in cardiovascular clinical trials. Traditionally formulated as the t -butyl amine (“erbumine”) salt, perindopril’s arginine salt has been FDA-approved in combination with amlodipine besylate. The arginine salt has the advantage of being more stable at higher temperatures or humidity. To demonstrate bioequivalence (using the standard FDA definition of 90% confidence intervals that are within 80-125% of the values seen with the reference product), the bioavailability of the two perindopril formulations was compared. After screening 121 healthy subjects, 30 (73% male, 38.9±9.5 years of age, 67% African American, BMI of 26.6±2.7 kg/m 2 ) signed informed consent, and were studied in a randomized, single-center, single-dose, open-label, 2-period, 2-way cross-over design with a 14-day washout period. After an overnight fast, perindopril was administered orally with 240 mL of water, and blood samples taken at defined time points. After dose-normalization (the arginine salt has a molecular weight 1.43-fold greater than that of the erbumine salt), all pharmacokinetic parameters for perindopril plasma concentrations were similar between treatments. Mixed model analysis of these parameters demonstrated bioequivalence (e.g., area under the time-plasma concentration curve: 10.2 vs. 10.5 hr•ng/mL/mg, P = 0.54). Very similar results with non-significant differences were also seen for the pharmacokinetics of perindoprilat (perindopril’s active metabolite): 33.3 vs. 38.3 hr•ng/mL/mg, P = 0.17. Two subjects did not complete the perindopril arginine arm of the study: one withdrew consent, and the other experienced a protocol deviation. No subjects experienced a serious adverse event or withdrew due to a treatment-emergent adverse event. Four subjects reported adverse events after perindopril arginine, and two subjects reported neck pain or presyncope after perindopril erbumine. After dose-normalization, these two formulations of perindopril meet all traditional criteria for AB rating and interchangeability.

scholarly journals No relevant pharmacokinetic drug–drug interaction between nintedanib and pirfenidone

2018 ◽  
Vol 53 (1) ◽  
pp. 1801060 ◽  
Author(s):  
Luca Richeldi ◽  
Sophie Fletcher ◽  
Huzaifa Adamali ◽  
Nazia Chaudhuri ◽  
Sabrina Wiebe ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Plasma Concentration ◽  
Geometric Mean ◽  
Maximum Plasma ◽  
Open Label ◽  
Time Curve ◽  
Drug Drug Interaction ◽  
Group 2 ◽  
Pharmacokinetic Drug ◽  
Group 1

Nintedanib and pirfenidone are approved treatments for idiopathic pulmonary fibrosis (IPF). This open-label, two-group trial investigated the pharmacokinetic drug–drug interaction between these two drugs in patients with IPF.Subjects not treated with antifibrotics at screening (group 1, n=20) received a single nintedanib dose (150 mg) followed by pirfenidone (titrated to 801 mg thrice daily) for 3 weeks, with a further single nintedanib dose (150 mg) on the last day (day 23). Subjects treated with pirfenidone at screening (group 2, n=17) continued to receive pirfenidone alone (801 mg thrice daily) for 7 days, then co-administered with nintedanib (150 mg twice daily) for a further 7 days, before single doses of both treatments on day 16.In group 1, adjusted geometric mean (gMean) ratios (with/without pirfenidone) were 88.6% and 80.6% for nintedanib area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax), respectively. In group 2, gMean ratios (with/without nintedanib) were 97.2% and 99.5% for pirfenidone AUC and Cmax, respectively. For all parameters, the 90% confidence intervals included 100%, suggesting similar exposure for administration alone and when co-administered. Both treatments were well tolerated.These data indicate there is no relevant pharmacokinetic drug–drug interaction between nintedanib and pirfenidone when co-administered in IPF patients.

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