In vitro metabolic profile and drug-drug interaction assessment of secnidazole, a high-dose 5-nitroimidazole antibiotic for the treatment of bacterial vaginosis.

A single-dose oral granule formulation of secnidazole 2 g (SOLOSEC ) has been approved in the US as a treatment for bacterial vaginosis. Available data on the likelihood of in vitro drug-drug and alcohol-drug interactions are limited. Secnidazole was incubated with cultured human hepatocytes over a range of concentrations (0-10 000 μmol/L) to assess metabolic profiling.

A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias.

Purpose: Daunorubicin can induce left ventricular dysfunction and QT interval prolongation. This study assessed the effects of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, on cardiac repolarization.

Methods: Twenty-six adults with acute leukemia were treated with CPX-351 for 1-2 induction cycles and ≤ 4 consolidation cycles.

Two Phase 1, Open-Label, Single-Dose, Randomized, Crossover Studies to Assess the Pharmacokinetics, Safety, and Tolerability of Orally Administered Granules of Secnidazole (2 g) in Healthy Female Volunteers Under Different Administration Conditions.

Bacterial vaginosis (BV) is the most common vaginal infection in reproductive-age women and a significant risk factor for sexually transmitted diseases and pregnancy complications. Standard 5- to 7-day antimicrobial treatments for BV are associated with high rates of recurrence and adverse events. SYM-1219 is a novel granule formulation containing 2 g of secnidazole, developed as an oral, single-dose BV treatment.

Thorough QT/QTc Evaluation of the Cardiac Safety of Secnidazole at Therapeutic and Supratherapeutic Doses in Healthy Individuals.

SYM-1219, a novel oral granule formulation of secnidazole, is under development as single-dose treatment for bacterial vaginosis. This 4-way, randomized, crossover study evaluated the effects of SYM-1219 on electrocardiographic (ECG) parameters in 52 healthy subjects. Subjects were administered single doses of SYM-1219, 2 g (proposed therapeutic dose), 6 g (supratherapeutic dose), placebo, and moxifloxacin (positive control).

Lack of a Pharmacokinetic Interaction Between SYM-1219 Granules Containing 2 Grams of Secnidazole and a Combined Oral Contraceptive in a Phase 1, Randomized, Open-Label Study in Healthy Female Volunteers.

Introduction: Bacterial vaginosis (BV) is a serious infection that is the most common vaginal infection in women of childbearing potential. SYM-1219 is a novel, granule formulation containing 2 g of secnidazole that is being developed as a single, oral dose to treat women with BV. Because many of the women diagnosed with BV use hormonal contraception, the effect of SYM-1219 on the pharmacokinetics (PK) of commonly prescribed oral contraceptive drugs, ethinyl estradiol (EE2), and norethindrone (NET) was evaluated.

Pharmacological In Vivo Inhibition of S-Nitrosoglutathione Reductase Attenuates Bleomycin-Induced Inflammation and Fibrosis.

Interstitial lung disease (ILD) characterized by pulmonary fibrosis and inflammation poses a substantial biomedical challenge due to often negative disease outcomes combined with the need to develop better, more effective therapies. We assessed the in vivo effect of administration of a pharmacological inhibitor of S-nitrosoglutathione reductase, SPL-334 (4-{[2-[(2-cyanobenzyl)thio]-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]methyl}benzoic acid), in a mouse model of ILD induced by intratracheal instillation of bleomycin (BLM). Daily i.

Pharmacokinetics and safety of FV-100, a novel oral anti-herpes zoster nucleoside analogue, administered in single and multiple doses to healthy young adult and elderly adult volunteers.

FV-100 is the prodrug of the highly potent anti-varicella zoster virus bicyclic nucleoside analogue CF-1743. To characterize the pharmacokinetics and safety of oral FV-100, 3 randomized, double-blind, placebo-controlled clinical trials were conducted: (i) a single-ascending-dose study in 32 healthy subjects aged 18 to 55 years (100-, 200-, 400-, and 800-mg doses) with an evaluation of the food effect in the 400-mg group; (ii) a multiple-ascending-dose study in 48 subjects aged 18 to 55 years (100 mg once daily [QD], 200 mg QD, 400 mg QD, 400 mg twice a day, and 800 mg QD for 7 days); and (iii) a 2-part study in subjects aged 65 years and older with a single 400-mg dose in 15 subjects and a 400-mg QD dosing regimen for 7 days in 12 subjects. FV-100 was rapidly and extensively converted to CF-1743, the concentration of which remained above that required to reduce viral activity by 50% for the 24-hour dosing period.

Population pharmacokinetics of telbivudine and determination of dose adjustment for patients with renal impairment.

Telbivudine is a new nucleoside analog indicated for the treatment of chronic hepatitis B infection. A population pharmacokinetic model was developed based on data pooled from 16 early phase studies in 363 healthy participants and patients. Telbivudine was administered as single and/or multiple doses of 25 to 1800 mg daily for up to 28 days.

Phase 1 and pharmacokinetic study of weekly docosahexaenoic acid-paclitaxel, Taxoprexin, in resistant solid tumor malignancies.

Purpose: To determine the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of weekly docosahexaenoic acid-paclitaxel (DHA-paclitaxel), a taxane fatty acid conjugate.

Experimental Design: Docosahexaenoic acid-paclitaxel was administered by 2-hour i.v.

The effect of multiple-dose, oral rifaximin on the pharmacokinetics of intravenous and oral midazolam in healthy volunteers.

Study Objective: To evaluate the potential of rifaximin, an oral nonabsorbed (< 0.4%) structural analog of rifampin, to induce human hepatic and/or intestinal cytochrome P450 (CYP) 3A enzymes, with use of a known CYP3A probe, midazolam.

Design: Prospective, randomized, open-label, two-period, crossover study.

An evaluation of the pharmacokinetics and pharmacodynamics of the histrelin implant for the palliative treatment of prostate cancer.

Seventeen patients with advanced prostate cancer were studied to evaluate the pharmacokinetics and pharmacodynamics of a hydrogel implant designed to deliver histrelin at a constant rate (50 microg/d) for 1 year. Serum histrelin levels were collected during the 52-week implantation period and after a second implant. Testosterone suppression was the primary pharmacodynamic endpoint, with treatment success defined as serum testosterone less than 50 ng/dL.

Methylphenidate bioavailability in adults when an extended-release multiparticulate formulation is administered sprinkled on food or as an intact capsule.

Objective: To determine the single-dose bioavailability of 20-mg Metadate CD (methylphenidate HCI, USP) Extended-Release Capsules sprinkled onto 1 level tablespoon (15 mL) of applesauce relative to an intact capsule under fasted conditions in healthy adults.

Method: This was a single-center, open-label, single-dose, randomized, two-way crossover study with a 6-day washout period between doses, in healthy male and female subjects (N= 26), aged 21-40 years. Plasma concentration-time data for methylphenidate were used to calculate the pharmacokinetic parameters for each treatment.