scholarly journals Influence of CYP2D6 and CYP3A5 Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Bisoprolol in Hypertensive Chinese Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Sze Wa Chan ◽  
Tanya T. W. Chu ◽  
Chung Shun Ho ◽  
Alice P. S. Kong ◽  
Brian Tomlinson ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
Chinese Patients ◽  
Open Label ◽  
Post Dose ◽  
Treatment Clinic ◽  
Liquid Chromatography Tandem Mass ◽  
The Common ◽  
Trough Levels ◽  
Trough Plasma

Purpose: This study was performed to investigate the effects of common polymorphisms in CYP2D6 and CYP3A5 on the plasma concentrations and antihypertensive effects of bisoprolol in hypertensive Chinese patients.Methods: One hundred patients with essential hypertension were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Clinic blood pressure (BP) and ambulatory BP (ABP) were measured after the placebo run-in and after 6 weeks treatment. Peak plasma concentrations of bisoprolol were measured at 3 h after the first dose and 3 h after the dose after 6 weeks treatment. Trough levels were measured before the dose after 6 weeks treatment. Bisoprolol plasma concentrations were measured with a validated liquid chromatography tandem mass spectrometry method. Six common polymorphisms in CYP2D6 and the CYP3A5*3 polymorphism were genotyped by TaqMan® assay.Results: After 6 weeks of treatment, clinic BP and heart rate were significantly reduced by 14.3 ± 10.9/8.4 ± 6.2 mmHg (P < 0.01) and 6.3 ± 7.6 BPM (P < 0.01), respectively. Similar reductions were seen in ABP values. Bisoprolol plasma concentration at 3 h after the first dose and 3 h post-dose after 6 weeks of treatment were significantly associated with baseline body weight (P < 0.001) but there was no significant effect of the CYP2D6 and CYP3A5 polymorphisms on these or the trough plasma concentrations. There was no significant association of the CYP2D6 and CYP3A5 polymorphisms or plasma bisoprolol concentrations with the clinic BP or ABP responses to bisoprolol.Conclusion: Bisoprolol 2.5 mg daily effectively reduced BP and HR. The common polymorphisms in CYP2D6 that were examined and the CYP3A5*3 polymorphism appear to have no benefit in predicting the hemodynamic response to bisoprolol in these patients.

scholarly journals Pharmacokinetics of a Novel Form of Biotin, Magnesium Biotinate, in Healthy Subjects (P06-027-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sara Perez Ojalvo ◽  
Sarah Sylla ◽  
James Komorowski
Keyword(s):  
Clinical Study ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Blood Levels ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Post Dose ◽  
Funding Sources ◽  
Study Results

Abstract Objectives Biotin, also known as vitamin B7, plays an important role in the metabolization of nutrients into energy. Magnesium biotinate (MgB) is a novel biotin compound that has been shown to be 40 times more soluble than D-Biotin. Preclinical evidence has shown that MgB is well absorbed into the bloodstream and tissues, particularly the brain, over time. The following pharmacokinetic study was carried out to further explore the absorption and bioavailability of MgB. Methods In an open-label clinical study, 30 healthy female subjects (18–45 years, BMI 18.0–29.9 kg/m2) were randomized to receive a single oral capsule containing one of the following doses of MgB (n = 10 per group): 1) 10 mg MgB, 2) 40 mg MgB, 3) 100 mg MgB. Serial blood samples were collected in K2-EDTA tubes at pre-dose (within 1 hour of dose) and at 0.5, 1.0, 1.5, 3.0 and 6.0 hours post-dose. Plasma samples were analyzed for biotin by LC/MS/MS. Pharmacokinetic data were calculated for each dose group. Results Study results showed that plasma biotin levels increased at 0.5, 1.0, 1.5, 3.0 and 6.0 hours post-dose for all groups. However, the largest biotin increase was seen in the 100 mg group (Figure 1). Peak plasma concentrations were observed as follows: 84.8 ng/mL 1 hour after a 10 mg dose, 214.6 ng/mL 1.5 hours after a 40 mg dose, and 508.5 ng/mL 1.5 hours after a 100 mg dose. Area under the curve values increased with increasing biotin dose level (10 mg: 210.0 ng*h/mL; 40 mg: 605.1 ng*h/mL; 100 mg: 1652.4 ng*h/mL). No adverse effects were observed. Conclusions Results from this single-dose pharmacokinetic clinical study demonstrate that magnesium biotinate is a bioavailable form of biotin, with increasing blood levels associated with increasing dose levels. Funding Sources This study was funded by JDS Therapeutics, LLC. Supporting Tables, Images and/or Graphs

Imatinib Plasma Concentration and Sokal Risk Score Are Independently Prognostic for Complete Cytogenetic Response (CCyR) in Patients with Chronic-Phase Chronic Myeloid Leukemia (CML-CP).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1935-1935 ◽  
Author(s):  
Richard A. Larson ◽  
Brian J. Druker ◽  
Francois Guilhot ◽  
Stephen G. O’Brien ◽  
Tillman Krahnke ◽  
...  
Keyword(s):  
Plasma Level ◽  
Odds Ratio ◽  
Risk Group ◽  
Plasma Concentrations ◽  
Laboratory Data ◽  
Risk Level ◽  
Stepwise Logistic Regression ◽  
Final Model ◽  
Trough Levels ◽  
Trough Plasma

Abstract Background: In the International Randomized Study of Interferon and STI571 (IRIS), 553 patients (pts) with newly diagnosed CML-CP were randomized to receive imatinib (IM) 400 mg/d. The 5-year analysis of these pts showed that first-line IM yielded an estimated 87% cumulative CCyR rate and an estimated 89% overall survival (OS) and was generally well tolerated (Druker et al, NEJM 2006). We analyzed the IM pharmacokinetic (PK) exposure and evaluated its effect on efficacy and safety parameters. Methods: Pts were grouped into quartiles according to IM trough plasma concentrations at steady state (day 29 of therapy; Q1 <647 ng/mL, Q2+Q3, and Q4 >1170 ng/mL). Adverse events (AEs) and discontinuations as well as CCyR (0% Ph+) rates were summarized based on these groups. A multivariate analysis was performed using stepwise logistic regression to examine whether IM plasma levels are prognostic for ability to achieve a CCyR independently of Sokal risk group, patient demographics, and laboratory data. Criteria for inclusion of variables into the statistical model was a P<0.15, and a P<0.05 was required for variables to remain in the final model. Results: Of 351 pts for whom PK samples were available, 105 (30%) have discontinued imatinib therapy: 41% of pts with low IM trough levels (Q1), 28% in Q2-Q3, and 23% in Q4. “Unsatisfactory therapeutic effect” was the most frequently cited reason for discontinuation in 18%, 15%, and 8% of pts in Q1, Q2-Q3, and Q4, respectively. Fluid retention, rash, myalgia, and anemia were more frequent relevant AEs, of any grade, among pts in Q4 vs Q1 group (76% vs 53%, 51% vs 32%, 30% vs 20% and 20% vs 8%, respectively), but these events did not translate into significantly higher discontinuations due to AEs. Muscle cramps, diarrhea, abdominal pain, headache, and hemorrhage were less frequent among pts with highest IM trough levels vs those with the lowest, suggesting that some AEs may be disease related. Overall, CCyR rates were 76% in pts with lowest IM trough levels (Q1), 85% in pts with intermediate levels (Q2-Q3), and 92% in pts with the highest trough levels (Q4) (P=0.013, Fisher’s exact test). Of pts with both Sokal risk and PK sample available, 50% were in the low risk group, 32% in the intermediate, and 18% in the high risk group; their CCyR rates were 94%, 84%, and 73%, respectively (P=0.002). Within each Sokal group, the prognostic effect of IM trough levels was most apparent in pts of intermediate risk, among whom 64% achieved CCyR in Q1 vs 94% in Q4 (P=0.015). Of all the evaluated prognostic variables, only Sokal risk and IM trough plasma level were prognostic for ability to achieve a CCyR. Based on the final multivariate model, for an increase by one Sokal risk level, the odds ratio of achieving a CCyR was 0.55 (95% CI, 0.32–0.93, P=0.027), while an increase by 250 ng/mL in IM trough yielded an odds ratio of 1.77 (1.22–2.56, P=0.003). No other factors met the selection criteria to remain in the final model. Conclusion: These results suggest that achieving an adequate IM plasma level is important for a good clinical response. Monitoring of IM plasma concentrations should be encouraged in patients with poor response.

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 Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study

2016 ◽  
Vol 175 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Gudmundur Johannsson ◽  
Hans Lennernäs ◽  
Claudio Marelli ◽  
Kevin Rockich ◽  
Stanko Skrtic
Keyword(s):  
Replacement Therapy ◽  
Plasma Concentrations ◽  
Open Label ◽  
Post Dose ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Endogenous Cortisol ◽  
Dual Release ◽  
Dose Proportional

Objective Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy was developed to provide a cortisol exposure−time profile that closely resembles the physiological cortisol profile. This study aimed to characterize single-dose pharmacokinetics (PK) of DR-HC 5–20mg and assess intrasubject variability. Methods Thirty-one healthy Japanese or non-Hispanic Caucasian volunteers aged 20−55 years participated in this randomized, open-label, PK study. Single doses of DR-HC 5, 15 (3×5), and 20mg were administered orally after an overnight fast and suppression of endogenous cortisol secretion. After estimating the endogenous cortisol profile, PK of DR-HC over 24h were evaluated to assess dose proportionality and impact of ethnicity. Plasma cortisol concentrations were analyzed using liquid chromatography−tandem mass spectrometry. PK parameters were calculated from individual cortisol concentration−time profiles. Results DR-HC 20mg provided higher than endogenous cortisol plasma concentrations 0−4h post-dose but similar concentrations later in the profile. Cortisol concentrations and PK exposure parameters increased with increasing doses. Mean maximal serum concentration (Cmax) was 82.0 and 178.1ng/mL, while mean area under the concentration−time curve (AUC)0−∞ was 562.8 and 1180.8h×ng/mL with DR-HC 5 and 20mg respectively. Within-subject PK variability was low (<15%) for DR-HC 20mg. All exposure PK parameters were less than dose proportional (slope <1). PK differences between ethnicities were explained by body weight differences. Conclusions DR-HC replacement resembles the daily normal cortisol profile. Within-subject day-to-day PK variability was low, underpinning the safety of DR-HC for replacement therapy. DR-HC PK were less than dose proportional – an important consideration when managing intercurrent illness in patients with adrenal insufficiency.

scholarly journals Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

2020 ◽  
Author(s):  
Li Xin ◽  
Chenjing Wang ◽  
Ting Li ◽  
Yanping Liu ◽  
Shuqin Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
Healthy Chinese ◽  
Chinese Subjects

Abstract Background: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.Results: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80~125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70±0.49) ng/mL, AUC0-t was (141.32±36.24) ng×h/mL and AUC0-∞ was (157.14±45.65) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83±0.52) ng/mL, AUC0-t was (153.62±33.96) ng×h/mL and AUC0-∞ was (173.05±41.78) ng×h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73±0.55) ng/mL, AUC0-t was (166.93±49.96) ng×h/mL and AUC0-∞ was (190.99±70.89) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87±0.81) ng/mL AUC0-t was (165.46±43.58) ng×h/mL and AUC0-∞ was (189.51±64.70) ng×h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.Conclusion: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

Randomized study comparing nab-paclitaxel with solvent-based paclitaxel in Chinese patients (pts) with metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1038-1038 ◽  
Author(s):  
Z. Guan ◽  
F. Feng ◽  
Q. L. Li ◽  
Z. Jiang ◽  
Z. Shen ◽  
...  
Keyword(s):  
Response Rate ◽  
Randomized Study ◽  
Metastatic Breast ◽  
Study Drug ◽  
Maximum Tolerated Dose ◽  
Chinese Patients ◽  
Open Label ◽  
Primary Endpoints ◽  
The Common ◽  
Favorable Safety

1038 Background: The results of a large clinical study comparing solvent-based paclitaxel 175 mg/m2 with 130-nM albumin-bound paclitaxel (nab-paclitaxel) 260 mg/m2 demonstrated that nab-paclitaxel had greater efficacy and a favorable safety profile in pts with MBC (Gradishar et al., JCO, 2005; 23:7794). The maximum tolerated dose of nab-paclitaxel was 300 mg/m2 infused over 30 minutes without premedication in Chinese pts with solid tumors (Teng et al., Ai Zheng, 2004;23:1431). The aim of this randomized study is to compare the response rates and to evaluate the safety of nab-paclitaxel with those of solvent-based paclitaxel in Chinese pts with MBC. Methods: In this open-label, multicenter study, 210 pts with MBC were assigned to either solvent-based paclitaxel 175 mg/m2 intravenously (IV) over 3 hours every 3 weeks (q3w) with standard premedication (steroids and antihistamines) or nab-paclitaxel 260 mg/m2 IV over 30 minutes q3w with no premedication for 1–6 cycles. The primary endpoints were the overall response rate (ORR, complete or partial response) and toxicity. Stable disease (SD) at =16 weeks was measured. All pts who received at least 1 dose of study drug were evaluable for study endpoints. Results: 210 pts (median age, 50 years; 70% postmenopausal) were enrolled from 29 June 2005 - 1 August 2006. Efficacy results are summarized in the Table . The common toxicities occurring at =20% were alopecia (78%), peripheral neuropathy (75%, 7% gr 3), neutropenia (65%), leucopenia (60%), myalgia (39%), arthralgia (23%), and nausea (21%) and were similar between groups (P = NS). Gr 3/4 neutropenia, measured on days 1 and 8, were similar between groups (p = 0.202). Conclusions: Compared to solvent- based paclitaxel, treatment with nab-paclitaxel was associated with a higher response rate and longer time to progression without increased toxicity. These comparative data in Chinese pts are almost identical to results previously reported in Caucasian pts (Gradishar et al, JCO, 2005). [Table: see text] [Table: see text]

Correlation of Pharmacokinetic Data with Cytogenetic and Molecular Response in Newly Diagnosed Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib - An Analysis of IRIS Study Data.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 429-429 ◽  
Author(s):  
Richard A. Larson ◽  
Brian J. Druker ◽  
Francois Guilhot ◽  
Stephen G. O’Brien ◽  
Insa Gathmann ◽  
...  
Keyword(s):  
Steady State ◽  
Active Metabolite ◽  
Trough Level ◽  
Plasma Concentrations ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Inter Quartile Range ◽  
Quartile Range ◽  
Trough Levels ◽  
Trough Plasma

Abstract A total of 551 pts with newly diagnosed CML-CP received imatinib (IM) 400 mg orally once daily as part of the IRIS study (O’Brien et al, NEJM 2003). We now summarize the correlation of clinical responses with the steady-state trough plasma concentrations (Cmin) of IM and its major active metabolite CGP74588. Cmin is a reflection of IM clearance and metabolism in CML pts. Trough PK samples (24 hrs post dose) were obtained in IM pts at Day 1 and steady state (Day 29). The plasma concentrations of IM and CGP74588 were determined by liquid chromatography/mass spectrometry. Estimated rates of complete cytogenetic response (CCyR - 0% Ph+) and major molecular response (MMR - ≥ 3 log reduction in BCR-ABL/BCR ratio from a standardized baseline value for untreated pts) were given for the lower and upper quartiles (below Q1=25th percentile, above Q3=75th percentile) and the inter-quartile range of PK trough levels. After 4 weeks of IM at 400 mg, the overall mean (±SD, CV%) steady-state trough levels (Cmin) for IM and CGP74588 (n=351 pts) were 979 (±530, 54.1%) and 242 (±106, 43.6%) ng/mL, respectively. Median (Q1–Q3, min-max) values (in ng/mL) were 879 (647–1170, 153–3910) for IM and 223 (169–291, 50–841) for CGP74588. Times to CCyR and MMR within CCyR pts were significantly different between the three groups of IM plasma exposure (low/intermediate/high; p&lt;0.025). The same was observed for CGP74588, since the parent drug and metabolite levels were highly correlated (0.77, Spearman correlation coefficient). Overall, Cmin of IM was statistically significantly higher in pts who achieved CCyR (1009±544 ng/mL vs. 812±409 ng/mL, p=0.0116). The estimated MMR rate among all pts was significantly lower in pts with low IM levels: only an estimated 59%x43%=25% of all pts with IM levels &lt;647 ng/mL achieved a MMR at 1 year (yr), compared to 40% of all other pts. By 4 yrs an estimated 53% achieved MMR despite low steady state Cmin levels compared with 80% for pts with high Cmin (and 72% for pts within inter-quartile range). CCyR and MMR rates [95% CI] within 1, 2, and 4 yrs by categories of IM trough plasma concentrations measured on Day 29 IM trough level &lt; 647 ng/mL (Q1) N = 87 647–1170 ng/mL N = 178 &gt; 1170 ng/mL (Q3) N = 86 CCyR (%) − 1 yr 59 [48, 70] 71 [64, 78] 73 [63, 83] − 2 yrs 73 [63, 83] 80 [73, 86] 84 [75, 92] − 4 yrs 81 [71, 91] 87 [81, 93] 89 [82, 96] MMR (%) in pts with CCyR − 1 yr 43 [28, 59] 56 [47, 66] 55 [41, 68] − 2 yrs 63 [49, 78] 78 [69, 86] 86 [76, 96] − 4 yrs 65 [50, 80] 83 [75, 91] 90 [81, 100] The trough plasma level following the 1st dose also showed a correlation with CCyR and MMR responses, but appeared to be less predictive than the trough level at steady state. Although all CML-CP pts had received 400 mg qd IM, CCyR and MMR rates at 1 to 4 yrs were depending on their IM trough level (24 hrs after the last dose) after 4 weeks of IM. Similar results were observed for the major active metabolite of IM. These results suggest that achieving and maintaining an adequate plasma concentration of IM is important for a good clinical response, and that therapeutic drug monitoring could be done by measuring trough levels at steady state conditions.

scholarly journals No Clinically Relevant Drug-Drug Interactions between Methadone or Buprenorphine-Naloxone and Antiviral Combination Glecaprevir and Pibrentasvir

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Matthew P. Kosloski ◽  
Weihan Zhao ◽  
Armen Asatryan ◽  
Jens Kort ◽  
Pierre Geoffroy ◽  
...  
Keyword(s):  
Nonstructural Protein ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Opiate Withdrawal ◽  
Protein Inhibitor ◽  
Open Label ◽  
Once Daily ◽  
Hcv Genotype 1 ◽  
Trough Plasma

ABSTRACT The combination of glecaprevir (formerly ABT-493), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (formerly ABT-530), an NS5A protein inhibitor, is being developed as treatment for HCV genotype 1 to 6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine-naloxone when coadministered with the glecaprevir-pibrentasvir combination in HCV-negative subjects on stable opioid maintenance therapy were investigated in a phase 1, single-center, two-arm, multiple-dose, open-label sequential study. Subjects received methadone (arm 1) or buprenorphine-naloxone (arm 2) once daily (QD) per their existing individual prescriptions alone (days 1 to 9) and then in combination with glecaprevir at 300 mg QD and pibrentasvir at 120 mg QD (days 10 to 16) each morning. Dose-normalized exposures were similar with and without glecaprevir and pibrentasvir for (R)- and (S)-methadone (≤5% difference) and for buprenorphine and naloxone (≤24% difference); the norbuprenorphine area under the curve was 30% higher with glecaprevir and pibrentasvir, consistent with maximum and trough plasma concentrations that increased by 21% to 25%. No changes in pupil response, short opiate withdrawal scale score, or desire for drugs questionnaire were observed when glecaprevir and pibrentasvir were added to methadone or buprenorphine-naloxone therapy. No dose adjustment is required when glecaprevir and pibrentasvir are coadministered with methadone or buprenorphine-naloxone.

scholarly journals Plasma Concentrations of Boswellic Acids in Fasting Healthy Humans Supplemented with a Water-Soluble Boswellia Extract (78% AKBA) vs. Reference Boswellia Extract (30% AKBA) (P06-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Barbara Davis ◽  
Krishanu Sengupta ◽  
Venkata Krishnaraju Alluri ◽  
Trimurtulu Golakoti
Keyword(s):  
Plasma Concentrations ◽  
Water Soluble ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Oral Ingestion ◽  
Post Dose ◽  
Geometric Means ◽  
Funding Sources ◽  
Healthy Humans

Abstract Objectives A randomized, open label, balanced, two-way crossover study compared the oral bioavailability and pharmacokinetic profiles of two Boswellia products standardized to 3-O-acetyl-11-Keto-β-boswellic acid (AKBA). Methods Twenty-two fasted male participants completed the study. They received a single oral-dose of water-soluble Boswellia extract 78% (LI51202F1) or the standard Boswellia extract 30% (5-Loxin) at 30 mg AKBA equivalent with 240 mL water on 2 separate occasions 12 days apart. Plasma AKBA and KBA were analyzed using a LC-MS/MS in pre- (0 hr) and post-dose (00.50, 01.00, 01.50, 02.00, 02.50, 03.00, 04.00, 08.00, 12.00 and 24.00 hrs) blood samples. Pharmacokinetic analysis was performed using WinNonlin® version 7.0 (Pharsight corporation, USA). Results Comparative analysis of the pharmacokinetic parameters showed LI51202F1 had higher (111.11%) Cmax for AKBA vs. 5-Loxin. The bioavailability indicated by Geometric means of AUC0-t and AUC0-∞ were 25.49% and 16.13% higher in LI51202F1 than 5-Loxin. Conclusions The present study demonstrates that oral ingestion of water soluble and standard Boswellia extracts resulted in similar bioavailability. Interestingly, the water-soluble version exhibited higher Cmax and AUC values, which could be attributed to the improved solubility of LI51202F1. Funding Sources Laila Nutraceuticals.

scholarly journals Pharmacokinetic Study of Human Immunodeficiency Virus Protease Inhibitors Used in Combination with Amprenavir

2001 ◽  
Vol 45 (12) ◽  
pp. 3663-3668 ◽  
Author(s):  
Brian M. Sadler ◽  
Catherine Gillotin ◽  
Yu Lou ◽  
Joseph J. Eron ◽  
William Lang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Protease Inhibitors ◽  
Pharmacokinetic Study ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Immunodeficiency Virus

ABSTRACT In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUCss] and 37% for peak plasma concentration at steady state [C max,ss]) and increased by indinavir (33% for AUCss). Nelfinavir significantly increased amprenavir minimum drug concentration at steady state (by 189%) but did not affect amprenavir AUCss orC max,ss. Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in amprenavir steady-state pharmacokinetic parameters, relative to those for amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.

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