scholarly journals Atogepant and sumatriptan: no clinically relevant drug–drug interactions in a randomized, open-label, crossover trial

2021 ◽  
Author(s):  
Ramesh Boinpally ◽  
Abhijeet Jakate ◽  
Matthew Butler ◽  
Antonia Periclou
Keyword(s):  
Plasma Concentration ◽  
Crossover Trial ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Geometric Mean ◽  
Open Label ◽  
Time Curve ◽  
Concentration Time ◽  
Pharmacokinetic Interactions ◽  
Randomized Crossover Study

Aim: To evaluate pharmacokinetic interactions of atogepant with sumatriptan, an open-label, randomized, crossover study was conducted. Patients & methods: Thirty healthy adults received atogepant 60 mg, sumatriptan 100 mg, or coadministered drugs. Primary end point was geometric mean ratios (GMRs) and 90% CIs of interventions for area under the plasma concentration–time curve from time 0 to t (AUC0-t) or infinity (AUC0-∞) and peak plasma concentration (Cmax). Results: Atogepant GMRs for AUC0-t and AUC0-∞ versus with sumatriptan were within 90% CI 0.80–1.25, indicating no interaction; atogepant Cmax was reduced by 22% (GMR: 0.78; 90% CI: 0.69–0.89) with sumatriptan. Sumatriptan GMRs for AUC0-t, AUC0-∞ and Cmax versus with atogepant were within 90% CI 0.80–1.25. Conclusion: Atogepant with sumatriptan had no clinically relevant pharmacokinetic interactions.

scholarly journals Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Satoshi Nakano ◽  
Shuhei Osaka ◽  
Yusuke Sabu ◽  
Kei Minowa ◽  
Saeko Hirai ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Peak Plasma ◽  
Oral Treatment ◽  
Peak Plasma Concentration ◽  
Open Label ◽  
Time Curve ◽  
Single Dose Study ◽  
Progressive Familial Intrahepatic Cholestasis

AbstractProgressive familial intrahepatic cholestasis (PFIC), a rare inherited disorder, progresses to liver failure in childhood. We have shown that sodium 4-phenylbutyrate (NaPB), a drug approved for urea cycle disorders (UCDs), has beneficial effects in PFIC. However, there is little evidence to determine an optimal regimen for NaPB therapy. Herein, a multicenter, open-label, single-dose study was performed to investigate the influence of meal timing on the pharmacokinetics of NaPB. NaPB (150 mg/kg) was administered orally 30 min before, just before, and just after breakfast following overnight fasting. Seven pediatric PFIC patients were enrolled and six completed the study. Compared with postprandial administration, an approved regimen for UCDs, preprandial administration significantly increased the peak plasma concentration and area under the plasma concentration-time curve of 4-phenylbutyrate by 2.5-fold (95% confidential interval (CI), 2.0–3.0;P = 0.003) and 2.4-fold (95% CI, 1.7–3.2;P = 0.005). The observational study over 3 years in two PFIC patients showed that preprandial, but not prandial or postprandial, oral treatment with 500 mg/kg/day NaPB improved liver function tests and clinical symptoms and suppressed the fibrosis progression. No adverse events were observed. Preprandial oral administration of NaPB was needed to maximize its potency in PFIC patients.

scholarly journals Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam and Meropenem Alone and in Combination following Single and Multiple Doses in Healthy Adult Subjects

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Christopher M. Rubino ◽  
Sujata M. Bhavnani ◽  
Jeffery S. Loutit ◽  
Elizabeth E. Morgan ◽  
Dan White ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Adult ◽  
Clinical Investigation ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Double Blind Study ◽  
Time Curve ◽  
Time Zero ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

ABSTRACTMeropenem-vaborbactam is a fixed combination of the novel β-lactamase inhibitor vaborbactam and the carbapenem antibiotic meropenem, developed for the treatment of serious infections caused by drug-resistant Gram-negative bacteria. The safety, tolerability, and pharmacokinetics (PK) of vaborbactam and meropenem following single and multiple ascending doses of each study drug administered alone or combined were evaluated in 76 healthy adult subjects in a randomized, placebo-controlled, double-blind study. Subjects were enrolled in 1 of 5 dose cohorts (receiving 250 to 2,000 mg vaborbactam and/or 1,000 to 2,000 mg meropenem) alone or in combination. No subjects discontinued the study due to adverse events (AEs), and no serious AEs were observed. The pharmacokinetics of meropenem and vaborbactam were similar when given alone or in combination; all evaluated plasma PK exposure measures (peak plasma concentration, area under the plasma concentration-time curve [AUC] from time zero to the last measurable concentration area under the plasma concentration-time curve, and AUC from time zero to infinity) were similar for the study drugs alone versus those in combination, indicating no pharmacokinetic interaction between meropenem and vaborbactam. Across all treatments, 47 to 64% of an administered meropenem dose and 75 to 95% of vaborbactam was excreted unchanged in the urine over 48 h postdose. Meropenem and vaborbactam, when given alone or in combination, have similar pharmacokinetic properties, with no plasma or urine PK drug-drug interactions, and are well tolerated. These findings supported further clinical investigation of the combination product. (This study is registered at ClinicalTrials.gov under registration no. NCT01897779.)

scholarly journals Comparative bioavailability study of phenytoin in healthy Nepalese volunteers

2019 ◽  
Vol 9 (1-s) ◽  
pp. 144-147
Author(s):  
DIllisher Rai ◽  
Gajendra Prasad Rauniar
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
P Value ◽  
Maximum Plasma ◽  
Time Curve ◽  
Oral Tablet ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

Our study aimed to assess and compare the bioavailability of Eptoin 100 mg and Epileptin 100mg tablets in Nepalese healthy volunteers. A randomized, two-treatment cross-over study with two weeks’ wash-out period was conducted in 12 healthy non-smoker and non-alcoholic Nepalese male volunteers over a period of 6 months in the department of Clinical Pharmacology and Therapeutic at B. P. Koirala Institute of Health Sciences, Dharan, Nepal after approval from the Institutional Review Committee. The participants were randomized using sealed envelope system and received a single 100 mg oral tablet of either of the formulations with a two week washout period. Blood samples were collected predose and at regular intervals postdose upto 72 hours. Plasma phenytoin levels were estimated by reverse phase high performance liquid chromatography. The analytical method was validated prior to the start of study. Cmax (Peak Plasma Concentration), Tmax (Time to achieve maximum Plasma Concentration), AUC0-72 (Area under plasma concentration time curve 0 to 72 hours), AUC0-∞ (Area under plasma concentration time curve 0 to ∞) and T½ (Elimination half-life) and Kel (Elimination rate constant) were calculated and 80-120% margin (90% confidence interval) was used to assess bioequivalence. ANOVA test was used to analyze the data at P-value of 0.05. All volunteers completed the study. The log-transformed values of Cmax, Tmax, AUC0-t, and AUC0-∞ of the both formulations were within the specified limits and were bioequivalent according to the regulatory definition of bioequivalence based on the rate and extent of absorption. Both products can be considered equally effective in medical practice. Keywords: Bioavailability, Bioequivalence, healthy volunteer, Nepal, phenytoin sodium.

scholarly journals Effects of the Antifungals Voriconazole and Fluconazole on the Pharmacokinetics of S-(+)- and R-(−)-Ibuprofen

2006 ◽  
Vol 50 (6) ◽  
pp. 1967-1972 ◽  
Author(s):  
Ville-Veikko Hynninen ◽  
Klaus T. Olkkola ◽  
Kari Leino ◽  
Stefan Lundgren ◽  
Pertti J. Neuvonen ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Respective Control ◽  
Control Value ◽  
Racemic Ibuprofen ◽  
The Mean

ABSTRACT Our objective was to study the effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of S-(+)- and R-(−)-ibuprofen. Twelve healthy male volunteers took a single oral dose of 400 mg racemic ibuprofen in a randomized order either alone, after ingestion of voriconazole at 400 mg twice daily on the first day and 200 mg twice daily on the second day, or after ingestion of fluconazole at 400 mg on the first day and 200 mg on the second day. Ibuprofen was ingested 1 h after administration of the last dose of voriconazole or fluconazole. Plasma concentrations of S-(+)- and R-(−)-ibuprofen were measured for up to 24 h. In the voriconazole phase, the mean area under the plasma concentration-time curve (AUC) of S-(+)-ibuprofen was 205% (P < 0.001) of the respective control value and the mean peak plasma concentration (C max) was 122% (P < 0.01) of the respective control value. The mean elimination half-life (t 1/2) was prolonged from 2.4 to 3.2 h (P < 0.01) by voriconazole. In the fluconazole phase, the mean AUC of S-(+)-ibuprofen was 183% of the control value (P < 0.001) and its mean C max was 116% of the control value (P < 0.05). The mean t 1/2 of S-(+)-ibuprofen was prolonged from 2.4 to 3.1 h (P < 0.05) by fluconazole. The geometric mean S-(+)-ibuprofen AUC ratios in the voriconazole and fluconazole phases were 2.01 (90% confidence interval [CI], 1.80 to 2.22) and 1.82 (90% CI, 1.72 to 1.91), respectively, i.e., above the bioequivalence acceptance upper limit of 1.25. Voriconazole and fluconazole had only weak effects on the pharmacokinetics of R-(−)-ibuprofen. In conclusion, voriconazole and fluconazole increased the levels of exposure to S-(+)-ibuprofen 2- and 1.8-fold, respectively. This was likely caused by inhibition of the cytochrome P450 2C9-mediated metabolism of S-(+)-ibuprofen. A reduction of the ibuprofen dosage should be considered when ibuprofen is coadministered with voriconazole or fluconazole, especially when the initial ibuprofen dose is high.

scholarly journals Pharmacokinetic Interactions between the Hormonal Emergency Contraception, Levonorgestrel (Plan B), and Efavirenz

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Monica L. Carten ◽  
Jennifer J. Kiser ◽  
Awewura Kwara ◽  
Samantha Mawhinney ◽  
Susan Cu-Uvin
Keyword(s):  
Geometric Mean ◽  
Liver Function Tests ◽  
Open Label ◽  
Time Curve ◽  
Geometric Means ◽  
Concentration Time ◽  
Plan B ◽  
Effective Contraception ◽  
Grade 3 ◽  
Hiv Negative

Objectives. Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC12) prior to and with efavirenz (EFV).Design. Prospective, open-label, single-arm, equivalence study.Methods. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters.T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed.Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8 ng*hr/mL, and maximum concentration (Cmax⁡) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities.Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV.

Exposure to Retinoic Acids in Non-Pregnant Women Following High Vitamin A Intake with a Liver Meal

2005 ◽  
Vol 75 (3) ◽  
pp. 187-194 ◽  
Author(s):  
Hartmann ◽  
Brørs ◽  
Bock ◽  
Blomhoff ◽  
Bausch ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Vitamin A ◽  
Safety Concern ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pregnant Female ◽  
Time Curve ◽  
High Vitamin ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

Animal liver is a rich source of vitamin A. Due to retinoic acid (RA) metabolites, vitamin A has a teratogenic potential and women are generally advised to avoid or to limit the consumption of liver during pregnancy. In a recent study in non-pregnant female volunteers following single and repeated doses of up to 30,000 IU/day of vitamin A as a supplement, the plasma concentration time curve of all-trans RA acid showed a diurnal-like profile. But, the overall exposure (AUC24h) remained essentially unaltered whereas AUC24h increased linearly with dose for 13-cis and 13-cis-4-oxo RA. The current study in non-pregnant female volunteers showed that a single high vitamin A intake with a liver meal (up to 120,000 IU) exhibited a similar diurnal-like plasma concentration time curve for all-trans RA and its overall exposure remained also unaltered, despite a temporary two-fold increase in peak plasma concentration. Concentrations of 13-cis and 13-cis-4-oxo RA increased several-fold after a liver meal, and exposure (AUC24h) increased three- to five-fold. Pooling our results with data in the literature revealed a linear relation between the mean AUC24h of 13-cis and 13-cis-4-oxo RA and vitamin A intake with liver. Metabolism to all-trans RA of vitamin A with liver seems not to be of safety concern. However, the observed increase of plasma concentrations and the dose-dependent increase in exposure to 13-cis and 13-cis-4-oxo RA support the current safety recommendations on vitamin A intake and suggest that women should be cautious regarding their consumption of liver-containing meals during pregnancy.

scholarly journals Open-Label Crossover Study of Primaquine and Dihydroartemisinin-Piperaquine Pharmacokinetics in Healthy Adult Thai Subjects

2014 ◽  
Vol 58 (12) ◽  
pp. 7340-7346 ◽  
Author(s):  
Borimas Hanboonkunupakarn ◽  
Elizabeth A. Ashley ◽  
Podjanee Jittamala ◽  
Joel Tarning ◽  
Sasithon Pukrittayakamee ◽  
...  
Keyword(s):  
Crossover Study ◽  
Hospital Admissions ◽  
Geometric Mean ◽  
Radical Cure ◽  
Open Label ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Pharmacokinetic Assessment ◽  
Adult Volunteers

ABSTRACTDihydroartemisinin-piperaquine is an artemisinin-based combination treatment (ACT) recommended by the WHO for uncomplicatedPlasmodium falciparummalaria, and it is being used increasingly for resistant vivax malaria where combination with primaquine is required for radical cure. The WHO recently reinforced its recommendations to add a single dose of primaquine to ACTs to reduceP. falciparumtransmission in low-transmission settings. The pharmacokinetics of primaquine and dihydroartemisinin-piperaquine were evaluated in 16 healthy Thai adult volunteers in a randomized crossover study. Volunteers were randomized to two groups of three sequential hospital admissions to receive 30 mg (base) primaquine, 3 tablets of dihydroartemisinin-piperaquine (120/960 mg), and the drugs together at the same doses. Blood sampling was performed over 3 days following primaquine and 36 days following dihydroartemisinin-piperaquine dosing. Pharmacokinetic assessment was done with a noncompartmental approach. The drugs were well tolerated. There were no statistically significant differences in dihydroartemisinin and piperaquine pharmacokinetics with or without primaquine. Dihydroartemisinin-piperaquine coadministration significantly increased plasma primaquine levels; geometric mean ratios (90% confidence interval [CI]) of primaquine combined versus primaquine alone for maximum concentration (Cmax), area under the concentration-time curve from 0 h to the end of the study (AUC0–last), and area under the concentration-time curve from 0 h to infinity (AUC0–∞) were 148% (117 to 187%), 129% (103 to 163%), and 128% (102 to 161%), respectively. This interaction is similar to that described recently with chloroquine and may result in an enhanced radical curative effect. (This study has been registered at ClinicalTrials.gov under registration no. NCT01525511.)

scholarly journals Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients

2016 ◽  
Vol 60 (10) ◽  
pp. 6252-6259 ◽  
Author(s):  
John S. Bradley ◽  
Jon Armstrong ◽  
Antonio Arrieta ◽  
Raafat Bishai ◽  
Shampa Das ◽  
...  
Keyword(s):  
Single Dose ◽  
Phase I ◽  
Pediatric Patients ◽  
Geometric Mean ◽  
Open Label ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Age Cohorts ◽  
Concentration Time ◽  
Systemic Antibiotic Therapy

ABSTRACTThis study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0–∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

scholarly journals Pharmacokinetics of Telbivudine in Healthy Subjects and Absence of Drug Interaction with Lamivudine or Adefovir Dipivoxil

2006 ◽  
Vol 50 (7) ◽  
pp. 2309-2315 ◽  
Author(s):  
Xiao-Jian Zhou ◽  
Barbara A. Fielman ◽  
Deborah M. Lloyd ◽  
George C. Chao ◽  
Nathaniel A. Brown
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Plasma Concentration ◽  
Healthy Subjects ◽  
Adefovir Dipivoxil ◽  
Geometric Mean ◽  
Time Curve ◽  
Concentration Time ◽  
Plasma Pharmacokinetics ◽  
Plasma Concentration Time Curve

ABSTRACT Two phase I studies were conducted to assess the plasma pharmacokinetics of telbivudine and potential drug-drug interactions between telbivudine (200 or 600 mg/day) and lamivudine (100 mg/day) or adefovir dipivoxil (10 mg/day) in healthy subjects. Study drugs were administered orally. The pharmacokinetics of telbivudine were characterized by rapid absorption with biphasic disposition. The maximum concentrations in plasma (C max) were reached at median times ranging from 2.5 to 3.0 h after dosing. Mean single-dose C max and area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) were 1.1 and 2.9 μg/ml and 7.4 and 21.8 μg · h/ml for the 200- and 600-mg telbivudine doses, respectively. Steady state was reached after daily dosing for 5 to 7 days. The mean steady-state C max and area under the plasma concentration-time curve over the dosing interval (AUCτ) were 1.2 and 3.4 μg/ml and 8.9 and 27.5 μg · h/ml for the 200- and 600-mg telbivudine repeat doses, respectively. The steady-state AUCτ of telbivudine was 23 to 57% higher than the single-dose values. Concomitant lamivudine or adefovir dipivoxil did not appear to significantly alter the steady-state plasma pharmacokinetics of telbivudine; the geometric mean ratios and associated 90% confidence interval (CI) for the AUCτ of telbivudine alone versus in combination were 106.3% (92.0 to 122.8%) and 98.6% (86.4 to 112.5%) when coadministered with lamivudine and adefovir dipivoxil, respectively. Similarly, the steady-state plasma pharmacokinetics of lamivudine or adefovir were not markedly affected by the coadministration of telbivudine; the geometric mean ratios and associated 90% CI, alone versus in combination with telbivudine, were 99.0% (87.1 to 112.4%) and 92.2% (84.0 to 101.1%), respectively, for the lamivudine and adefovir AUCτ values. Moreover, the combination regimens studied were well tolerated in all subjects. The results from these studies provide pharmacologic support for combination therapy or therapy switching involving telbivudine, lamivudine, and adefovir dipivoxil for the treatment of chronic hepatitis B virus infection.

Interaction of Metoprolol, Propranolol and Atenolol with Cimetidine

1982 ◽  
Vol 63 (s8) ◽  
pp. 451s-453s ◽  
Author(s):  
W. Kirch ◽  
H. Spahn ◽  
H. Köhler ◽  
E. Mutschler
Keyword(s):  
Plasma Concentration ◽  
Healthy Volunteers ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Concurrent Administration ◽  
Time Curve ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

1. Pharmacokinetics of metoprolol, propranolol and atenolol were investigated in six healthy volunteers after 7 days of oral monotherapy with these drugs and after 7 days concurrent administration, with each of these β-adrenoceptor antagonists with cimetidine. 2. Cimetidine did not interact with atenolol, whereas mean peak plasma concentrations of metoprolol were increased by 70%, and those of propranolol by 95% with concurrent administration of cimetidine (P < 0.05). 3. The area under the plasma concentration-time curve for propranolol and metoprolol was similarly increased (P < 0.05).

Sign in / Sign up

Export Citation Format

Share Document