Common deficiencies with bioequivalence submissions in abbreviated new drug applications assessed by FDA.

Purpose: A generic product must meet the standards established by the Food and Drug Administration (FDA) to be approved for marketing in the USA. FDA approves a generic product for marketing if it is proved to be therapeutically equivalent to the reference product. Bioequivalence (BE) between a proposed generic product and its corresponding reference product is one of the major components of therapeutic equivalence.

High performance liquid chromatographic measurement of iothalamate in human serum and urine for evaluation of glomerular filtration rate.

A simple and sensitive HPLC-UV assay was developed for the measurement of iothalamate (IOT) in human serum and urine. Chromatographic separation was achieved using an embedded-carbamate-group bonded RP18 column and mobile phase consisting of 50 mM monobasic sodium phosphate and methanol (90:10, v/v) without the addition of ion-pair reagents. The assay demonstrated a high analytical reliability within the IOT concentration range of 1-150 microg/ml in serum and 25-1500 microg/ml in urine.

Prevalence of abnormal liver-associated enzymes in cocaine experienced adults versus healthy volunteers during phase 1 clinical trials.

The frequency and nature of elevation of liver-associated enzymes (LAE) are important safety endpoints in Phase 1 clinical trials of new anti-cocaine agents, yet very little information is available on the prevalence of abnormal LAE in cocaine experienced adults. The aim of this retrospective study was to investigate the alterations of liver-associated enzymes (LAE) aspartate- (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin in healthy "normal" (HN) and cocaine experienced (actively using cocaine preadmission (CE)) adults participating in long term inpatient clinical trials. We examined LAE values collected from 3 inpatient Phase 1 trials of anti-cocaine agents.

Pyridostigmine, diethyltoluamide, permethrin, and stress: a double-blind, randomized, placebo-controlled trial to assess safety.

Objective: To determine whether short-term human exposure to pyridostigmine bromide, diethyltoluamide, and permethrin, at rest or under stress, adversely affects short-term physical or neurocognitive performance.

Participants And Methods: A multicenter, prospective, double-blind, placebo-controlled crossover trial exposing 64 volunteers to permethrin-impregnated uniforms, diethyltoluamide-containing skin cream, oral pyridostigmine, and corresponding placebos was performed. Each participant had 4 separate sessions, ensuring exposure to all treatments and placebos under both stress and rest conditions in random order.

Rapid determination of N,N-diethyl-m-toluamide and permethrin in human plasma by gas chromatography-mass spectrometry and pyridostigmine bromide by high-performance liquid chromatography.

A rapid and highly sensitive gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of N,N-diethyl-m-toluamide (DEET) and permethrin with (2)H(10)-phenanthrene (98 atom %) as an internal standard and a separate external standard high-performance liquid chromatography (HPLC) method for pyridostigmine bromide (PB) determination in human plasma were developed and validated. The GC-MS method for DEET and permethrin quantification utilizes a one-step extraction with tert-butylmethylether. The HPLC method for PB quantification involves a solid-phase extraction and UV detection.

Initial evaluation of N,N-diethyl-m-toluamide and permethrin absorption in human volunteers under stress conditions.

Objectives: This was a pilot study to determine (1) whether it is feasible to effectively blind human subjects to the presence of the insect repellents N,N-diethyl-m-toluamide (DEET) and permethrin; (2) whether DEET affects the absorption of permethrin; and (3) whether combat videotape viewing and mental arithmetic are stressful.

Methods: Ten volunteers were exposed to DEET, permethrin, and stress (1-hour combat videotape plus mental arithmetic) in a double-blind, randomized, placebo-controlled trial. Outcome measurements included hemodynamics, plasma DEET and permethrin levels, and questionnaires to assess blinding.