Serum testosterone levels in non-dosed females after secondary exposure to 1.62% testosterone gel: effects of clothing barrier on testosterone absorption.

Objective: To evaluate secondary exposure of testosterone transferred to females from a male partner, dosed with 1.62% testosterone gel after direct skin-to-skin contact with the application site, and to investigate the effect of wearing a t-shirt on testosterone transfer.

Research Design And Methods: Across three studies, a total of 72 healthy males applied 5.

Effect of application site, clothing barrier, and application site washing on testosterone transfer with a 1.62% testosterone gel.

Objectives: To evaluate the effect of application site location, clothing barrier, and application site washing on testosterone transfer from males dosed with 1.62% testosterone gel to female partners.

Research Design And Methods: Open-label, randomized, parallel group, crossover study performed in 24 healthy male/female couples.

Effects of skin washing on systemic absorption of testosterone in hypogonadal males after administration of 1.62% testosterone gel.

Objective: The impact of washing on the pharmacokinetics, systemic absorption and residual testosterone on the skin after application of a 1.62% testosterone gel was investigated in an open-label, randomized, three-way crossover study in hypogonadal men.

Research Design And Methods: Twenty-four hypogonadal men (total testosterone <300 ng/dL) applied 5 g of 1.

Pharmacokinetics and relative bioavailability of absorbed testosterone after administration of a 1.62% testosterone gel to different application sites in men with hypogonadism.

Objective: To determine the pharmacokinetics, bioavailability, and safety of a new formulation (1.62%) of testosterone gel that produces eugonadal serum testosterone levels with use of a lower amount of gel than the currently available 1% gels.

Methods: In an open-label, randomized, 3-way crossover study, 36 male patients with hypogonadism applied 5 g of 1.

Challenges of characterizing proarrhythmic risk due to QTc prolongation induced by nonadjuvant anticancer agents.

Background: Drug-induced QTc prolongation is becoming increasingly important in oncology since novel therapies result in prolonged survival of cancer patients already predisposed to cardiotoxicity.

Methods: We review the challenges of implementing the ICH E14 guidance in oncology and propose an integrated approach to QTc risk assessment of nonadjuvant anticancer agents (NAAs), with quantitative outcome criteria.

Results: We recommend informed use of non-clinical cardiac safety pharmacology results, some degree of robust ECG assessments in early phase studies, a dedicated QTc study in cancer patients conducted at the appropriate time pre-, peri-, or post-approval (with the design and timing agreed upon with regulatory agencies), and ECG monitoring in late-phase studies commensurate with the outcome of previous QTc studies.

The effect of mild and moderate hepatic impairment on the pharmacokinetics of valdecoxib, a selective COX-2 inhibitor.

Purpose: This study evaluated the effects of varying degrees of hepatic impairment on the pharmacokinetics and safety of valdecoxib following single and multiple dosing.

Methods: This was an open-label, randomised, parallel group study in 12 subjects with mild hepatic impairment (Child-Pugh Class A) and in 13 with moderate hepatic impairment (Child-Pugh Class B) matched for age, weight, sex, and smoking status; there were two control groups of 12 healthy volunteers, one for each study group. All subjects received a single dose of valdecoxib 20 mg on day 1 and valdecoxib 20 mg twice daily on days 4-7, followed by a single morning dose on day 8.

Valdecoxib, a COX-2-specific inhibitor, does not affect cardiac repolarization.

This double-blind, four-way crossover study assessed the effect of valdecoxib on the QTc interval duration in 25 male and 9 female healthy adults. Subjects received placebo or 40 mg, 80 mg, or 120 mg valdecoxib once daily for 5 days. Serial ECGs were obtained for 24 hours before the first treatment (baseline) and on the 5th day of each treatment.

Assessment of normal and tumor tissue uptake of MAG-CPT, a polymer-bound prodrug of camptothecin, in patients undergoing elective surgery for colorectal carcinoma.

Purpose: MAG-camptothecin (MAG-CPT) is the lead compound of a novel drug delivery system in which an active cytotoxic moiety, camptothecin (CPT), is covalently linked to a soluble polymeric carrier (MAG) to form an inactive prodrug. The mechanism of action of CPT remains unaltered, but the delivery system is thought to allow the carrier-bound drug to accumulate in tumor tissues and release the active CPT locally. This proof-of-concept clinical study was designed to determine whether MAG-CPT was preferentially delivered to or retained in tumor tissue compared to adjacent normal tissue or plasma, and to estimate the degree of intratissue release of CPT.

The pharmacokinetics of sumatriptan when administered with norethindrone 1 mg/ethinyl estradiol 0.035 mg in healthy volunteers.

Background: Because the majority of migraineurs are young women in their peak reproductive years, it is important to understand the possible effects on the pharmacokinetics of both medications when sumatriptan is coadministered with an oral contraceptive (OC).

Objectives: The primary objective of this study was to assess the effect of multiple dosing of the OC norethindrone 1 mg/ethinyl estradiol 0.035 mg (NE/EE) on the single-dose pharmacokinetics of sumatriptan in healthy volunteers.