Bioequivalence of Two Formulations of a Single Oral Dose of 500-mg Azithromycin Granules: A Randomized, Open-Label, Two-Period Crossover Study in Healthy Han Chinese Volunteers

Abstract Background Antimicrobial resistance to available oral antibiotics is becoming progressively more common, precipitating the need for additional treatment options as step-down from initial intravenous (IV) therapy as well as for treatment of infections in the community. Sulopenem (CP-70,429) is a thiopenem antibiotic active against quinolone non-susceptible and ESBL-producing Enterobacteriaceae. As the key pharmacokinetic-pharmacodynamic variable correlating with efficacy for penem antibiotics is time above minimum inhibitory concentration (T > MIC), we examined the utility of probenecid, an OAT-1 inhibitor of β-lactam excretion, on the pharmacokinetic (PK) parameters for the oral prodrug of sulopenem, sulopenem etzadroxil Methods Twelve healthy males and females received a single oral dose of 500 mg sulopenem etzadroxil as powder in bottle either alone or co-administered with a single oral dose of probenecid 500 mg in a crossover design with a washout period of 6 days. All doses were administered under fasting conditions. Blood samples for plasma PK analysis were collected and PK parameters for sulopenem, the parent compound of sulopenem etzadroxil, were determined. Results Treatment Conclusion Probenecid increases the AUC of sulopenem by 28% in the fasted state and extends the mean time over MIC. Disclosures M. Dunne, Iterum Therapeutics: Employee and Shareholder, Salary. S. Aronin, Iterum Therapeutics: Employee and Shareholder, Salary. E. Dunzo, Parexel: Consultant, Consulting fee. S. Puttagunta, Iterum Therapeutics: Employee and Shareholder, Salary.

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Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-019-04015-w ◽

2019 ◽

Vol 85 (2) ◽

pp. 391-399 ◽

Cited By ~ 6

Author(s):

Song Mu ◽

Zhiyu Tang ◽

William Novotny ◽

Manal Tawashi ◽

Ta-Kai Li ◽

...

Keyword(s):

Steady State ◽

Oral Dose ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Single Oral Dose ◽

Kinase Inhibitor ◽

Clinical Activity ◽

Bruton’S Tyrosine Kinase ◽

Open Label ◽

Bruton's Tyrosine Kinase

Abstract Purpose Zanubrutinib (BGB-3111) is a potent Bruton’s tyrosine kinase inhibitor with promising clinical activity in B-cell malignancies. Zanubrutinib was shown to be mainly metabolized through cytochrome P450 3A (CYP3A) in vitro. We evaluated the effect of steady-state rifampin (a strong CYP3A inducer) and steady-state itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics (PK), safety, and tolerability of zanubrutinib in healthy Asian and non-Asian subjects. Methods In this open-label, two-part clinical study, 20 participants received a single oral dose of zanubrutinib (320 mg) and oral rifampin (600 mg) in Part A, and 18 participants received a single oral dose of zanubrutinib (20 mg) and oral itraconazole (200 mg) in Part B. Serial blood samples were collected after administration of zanubrutinib alone and zanubrutinib in combination with rifampin or itraconazole for the measurement of PK parameters. Results Coadministration with rifampin decreased AUC0–∞ of zanubrutinib by 13.5-fold and Cmax by 12.6-fold. Coadministration with itraconazole increased the AUC0–∞ of zanubrutinib by 3.8-fold and Cmax by 2.6-fold. The PK of zanubrutinib was consistent between Asian and non-Asian subjects, and zanubrutinib was well tolerated in this study. Conclusions These results confirm that zanubrutinib is primarily metabolized by CYP3A in humans. The PK of zanubrutinib was comparable between Asian and non-Asian subjects and, therefore, no dose modifications are necessary for zanubrutinib in these ethnic populations.

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Effects of the Chinese Herbal Formulation (Liu Wei Di Huang Wan) on the Pharmacokinetics of Isoflavones in Postmenopausal Women

BioMed Research International ◽

10.1155/2015/902702 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Wirin Limopasmanee ◽

Sunee Chansakaow ◽

Noppamas Rojanasthien ◽

Maleeya Manorot ◽

Chaichan Sangdee ◽

...

Keyword(s):

Plasma Concentration ◽

Oral Dose ◽

Single Oral Dose ◽

Postmenopausal Women ◽

Pharmacokinetic Parameters ◽

Soy Milk ◽

Open Label ◽

Fixed Sequence ◽

Time Curve ◽

Oral Doses

A combination of soy isoflavones andLiu Wei Di Huang Wan(LWDHW) is potentially effective for postmenopausal women with intolerable vasomotor episodes who are not suitable candidates for hormonal therapy. The objective of this open-label, three-phase, crossover study was to determine the influence of both single and multiple oral doses of LWDHW on isoflavone pharmacokinetics in healthy postmenopausal women. Eleven subjects were assigned to receive the following regimens in a fixed sequence with washout periods of at least one week: Phase A, a single oral dose of soy milk; Phase B, a single oral dose of soy milk coadministered with LWDHW; and Phase C, multiple oral doses of LWDHW for 14 days followed by a single oral dose of soy milk. Blood samples were collected and mixed withβ-glucuronidase/sulfatase to hydrolyze isoflavone conjugates to their respective aglycones (i.e., daidzein and genistein) and were determined using high performance liquid chromatography. The pharmacokinetic parameters analyzed were maximal plasma concentrationCmax, time to reach peak concentrationTmax, area under the plasma concentration-time curve (AUC), and half-life (t1/2). The results found no statistically significant differences in pharmacokinetic parameters of daidzein and genistein among the three regimens.

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856 Final Results of Phase II, Open Label, Study Investigating Polyp and Adenoma Detection Rate After Single Oral Dose of Methylene Blue MMx® Modified Release Tablets Administered to Subjects Undergoing Outpatients Colonoscopy

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2013.04.137 ◽

2013 ◽

Vol 77 (5) ◽

pp. AB175 ◽

Cited By ~ 3

Author(s):

Alessandro Repici ◽

Elisa Chiara Ferrara ◽

Eva M. Vitetta ◽

Lucia Fini ◽

Camilla Ciscato ◽

...

Keyword(s):

Methylene Blue ◽

Oral Dose ◽

Single Oral Dose ◽

Phase Ii ◽

Detection Rate ◽

Modified Release ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Adenoma Detection

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Efficacy of a single oral dose artesunate plus sulfalene/pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni in Kenyan children: randomised, exploratory, open-label trial

10.21203/rs.3.rs-75604/v1 ◽

2020 ◽

Author(s):

Erick M.O Muok ◽

Vincent O. Were ◽

Charles O. Obonyo

Keyword(s):

Single Dose ◽

Oral Dose ◽

Single Oral Dose ◽

Cure Rate ◽

Open Label ◽

Serious Adverse Event ◽

Western Kenya ◽

Potential Alternative ◽

Periodic Administration ◽

To Receive

Abstract Background: The global control strategy for schistosomiasis is the periodic administration of praziquantel. Schistosomes have developed reduced susceptibility to praziquantel. Artemisinin-based drug combinations are promising alternatives to praziquantel, but it is unclear whether a single dose of an artemisinin-based drug combination is as effective and safe as praziquantel. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene/pyrimethamine in the treatment of schistosomiasis. Methods: An exploratory, open-label randomized trial, was carried out in Rarieda sub-County, western Kenya to compare the efficacy of a single oral dose of artesunate plus sulfalene/pyrimethamine (12mg/kg of artesunate) to a standard single dose of praziquantel (40mg/kg) in the treatment of school children (aged 6 to 15 years) with S. mansoni infection. The primary outcomes were cure and egg reduction rates on day 28 after treatment in the per-protocol population.Results: A total of 73 S. mansoni infected children were included and randomized to receive either artesunate plus sulfalene/pyrimethamine (n=39) or praziquantel (n=34). 67 children completed the study. The cure rate was 69.4% (25/36) in the artesunate plus sulfalene/pyrimethamine group and 80.6% (25/31) in the praziquantel group (p=0.294). Egg reduction rates were 96.2% in the artesunate plus sulfalene/pyrimethamine group and 82.9% in the praziquantel group (p=0.339). Ten children treated with praziquantel developed adverse events compared with four in the artesunate plus sulfalene/pyrimethamine group. There was no serious adverse event. Conclusion: A single oral dose of artesunate plus sulfalene/pyrimethamine was safe and as efficacious as praziquantel in the treatment of S. mansoni in Kenyan children. These results should be confirmed in larger randomized controlled trials. Combination treatment with praziquantel plus artemisinin-based combination therapies may be a potential alternative for improving praziquantel efficacy and transmission control. Trial Registration: ClinicalTrials.gov, number NCT01054651.

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Influence of mild and moderate hepatic impairment on the pharmacokinetics (PK) of the pan-HER inhibitor dacomitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2568 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2568-2568 ◽

Cited By ~ 1

Author(s):

Nagdeep Giri ◽

Anna Plotka ◽

Yali Liang ◽

Tanya Boutros ◽

Grace Ni ◽

...

Keyword(s):

Liver Function ◽

Oral Dose ◽

Single Oral Dose ◽

Hepatic Impairment ◽

Hepatic Function ◽

Moderate Hepatic Impairment ◽

Open Label ◽

Post Dose ◽

Normal Hepatic Function ◽

Mild Impairment

2568 Background: Dacomitinib (D) is a highly selective irreversible small molecule inhibitor of the HER family of tyrosine kinases in clinical development for NSCLC.Prior clinical studies of D, which has minimal renal excretion (~3%), enrolled pts with protocol-defined adequate liver function. Liver metastases, leading to abnormal liver function tests, are common in pts with advanced cancer. This study evaluated the effect of hepatic impairment on PK and safety of D following a single oral dose in subjects with mild or moderate hepatic impairment. Methods: In this phase I, open-label, parallel group study, 25 subjects with either normal hepatic function (n=8) or mild (Child-Pugh A; n=8) or moderate (Child-Pugh B; n=9) hepatic impairment were administered a single, oral dose of D (30 mg). PK samples were collected at intervals up to 264 h post-dose and safety was assessed by laboratory abnormalities, physical examination, vital signs, ECGs, and AE monitoring. Analysis of variance was performed on natural log-transformed AUC and Cmaxto estimate adjusted mean differences between groups and 90% CIs, which were exponentiated to produce the adjusted GMR and 90% CI of the ratios. Results: GMR and 90% CI for AUCinf and Cmax (preliminary analyses) are listed.Mean D exposure (AUCinf and Cmax) was similar in subjects with normal hepatic function and those with mild impairment. Moderate hepatic impairment decreased D exposure by 15% and 20% for AUCinf and Cmax, respectively, vs normal hepatic function, but the 90% CI was relatively wide, and included 1. Plasma protein binding of D was similar in the 3 groups. No clinically significant treatment-related AEs were reported. Conclusions: Mean D exposure (AUCinf and Cmax) was similar in subjects with normal hepatic function and those with mild impairment. Mean D exposure appeared slightly lower in subjects with moderate impairment. Dose reduction of D in subjects with mild or moderate hepatic impairment may not be necessary. A single 30 mg dose of D was well tolerated in subjects with mild or moderate hepatic impairment. Clinical trial information: NCT01571388. [Table: see text]

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