Thalidomide as a novel therapeutic agent: new uses for an old product.

Thalidomide and its immunomodulatory analogues have numerous effects on the body's immune system, including potential anti-cancer and anti-inflammatory activities. Thalidomide is currently used experimentally to treat various cancers, dermatological, neurological and inflammatory diseases. This drug is approved in the USA for cutaneous manifestations of lepromatous leprosy and is in Phase III trials for multiple myeloma.

Effects of thalidomide on developmental, peri- and postnatal function in female New Zealand white rabbits and offspring.

The present study determined effects of thalidomide on three successive generations of New Zealand White rabbits after oral dosing to F0 maternal rabbits during the later third of gestation (post major organogenesis) and lactation. One hundred and twenty four time-mated F0 rabbits (31/dose) were gavaged with 0, 30, 150, or 500 mg/kg thalidomide from gestation day 18 (DG 18) to lactation day 28 (DP or day postpartum 28) for approximately 42 days. At 6 months, 12 F1 males and 12 F1 females were randomly paired within each dose group and mated.

Clinical pharmacokinetics of thalidomide.

Thalidomide is a racemic glutamic acid derivative approved in the US for erythema nodosum leprosum, a complication of leprosy. In addition, its use in various inflammatory and oncologic conditions is being investigated. Thalidomide interconverts between the (R)- and (S)-enantiomers in plasma, with protein binding of 55% and 65%, respectively.

Effects of thalidomide on reproductive function and early embryonic development in male and female New Zealand white rabbits.

Background: The present work was performed to determine the effect of thalidomide exposure on reproductive function and early embryonic development.

Methods: Twenty-five female New Zealand White rabbits were orally gavaged with 0, 10, 50, or 100 mg/kg/day thalidomide 14 days prior to mating through to gestation day 7 for a total of 22 days. Treated females were Caesarean-sectioned approximately 29 days after the date of attempted mating.

A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects.

Attention deficit hyperactivity disorder (ADHD) in children is effectively treated by racemic oral methylphenidate (dl-MPH). The d-isomer (d-MPH) has been developed as an improved treatment for ADHD since only half the racemic dose is used. This study, performed in healthy subjects, assessed the effect of food on the pharmacokinetics of dexmethylphenidate hydrochloride (d-MPH HCl) in a single dose (2 x 10-mg tablets), two-way crossover with d-MPH administered to subjects in both a fasting state or after a high-fat breakfast.

D-methylphenidate and D,L-methylphenidate are not developmental toxicants in rats and rabbits.

Background: D,L-threo-Methylphenidate (D,L-MPH) is marketed currently for attention deficit hyperactivity disorder in children. D-threo-methylphenidate (dexmethylphenidate; D-MPH) is a refined formulation of D,L-methylphenidate containing only the active enantiomer and was recently approved in the U.S.

A 90-day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in beagle dogs.

d-Methylphenidate (d-MPH) was approved as a treatment for attention deficit hyperactivity disorder (ADHD) in children. The repeated-dose toxicity of the d enantiomer of d,l-methylphenidate (d,l-MPH) was assessed in male and female Beagle dogs. Dogs were orally dosed twice a day in equally divided doses 6 hours apart for total daily doses of 1, 3, and 10 mg/kg/day d-MPH or 20 mg/kg/day d,l-MPH for 90 days, followed by a 30-day recovery period.

D-Methylphenidate is non-genotoxic in in vitro and in vivo assays.

D-Methylphenidate (dexmethylphenidate; D-MPH) and its racemate D,L-methylphenidate (D,L-MPH) are currently prescribed for the chronic treatment of attention deficit hyperactivity disorder (ADHD) in children. Studies have shown that D-MPH is the pharmacologically active enantiomer for ADHD and is therefore the preferred drug for the treatment of ADHD symptoms. Although studies on the mutagenicity of D,L-MPH have been conducted, similar data for D-MPH are lacking.

Chiral inversion of the second generation IMiD CC-4047 (ACTIMID ) in human plasma and phosphate-buffered saline.

CC-4047 is a racemic second-generation immunomodulatory drug currently in clinical development for various oncologic indications. It has potent effects on key cytokines including tumor necrosis factor-alpha, interleukin (IL-10), and interferon (IFN-gamma). The S-isomer of CC-4047 has been reported to be the more potent enantiomer of the racemate.

Neurobehavioral effects of racemic threo-methylphenidate and its D and L enantiomers in rats.

D,L-methylphenidate (Ritalin) is used to treat attention deficit hyperactivity disorder (ADHD) in children. The therapeutic effect is predominantly due to the d enantiomer. Dexmethylphenidate (D-MPH; Focalin) was therefore developed for its better therapeutic index.

Thalidomide in the treatment of leprosy.

Leprosy is a chronic infection of the skin and nerves caused by Mycobacterium leprae. Erythema nodosum leprosum (ENL) is a reactive state in lepromatous leprosy. Thalidomide has been used to treat ENL since the 1960s.

The perinatal and postnatal toxicity of D-methylphenidate and D,L-methylphenidate in rats.

D-methylphenidate is an enantiomer of D,L-methylphenidate and was developed as an improved treatment for attention deficit hyperactivity disorder (ADHD) in children. The current study was performed to assess the potential perinatal and postnatal toxicity of both compounds in rats. About 125 presumed pregnant rats were assigned to five dose groups of 25 each.

Sensitive and rapid method for the determination of thalidomide in human plasma and semen using solid-phase extraction and liquid chromatography-tandem mass spectrometry.

Liquid chromatography-tandem mass spectrometric assays were developed for the sensitive, rapid and high throughput bioanalyses of thalidomide in human plasma and semen. The matrices were first stabilized with 0.025 M Sorensen's citrate buffer at pH 1.