Stability of fludrocortisone acetate solutions prepared from tablets and powder.

To assess the stability of fludrocortisone acetate oral solutions prepared from tablets and powder at three temperatures over a 60-days period. Solutions of fludrocortisone acetate 40 microg/ml were prepared from commercially available 0.05-mg tablets and powder in ethanol 17% v/v. They stored in an amber glass prescription bottles at +4, +23 and +40 degrees C shielded from light. The concentrations of fludrocortisone acetate were determined in duplicate by high-performance liquid chromatography at 0, 1, 7, 14, 30, 50 and 60 days. The initial and final pH of solutions were compared. The recovery of fludrocortisone acetate from tablets was determined. The times (t(90)) needed for fludrocortisone acetate to fall to 90% of it's initial concentration were calculated by a linear regression analysis to allow the determination of the expired dates. The recovery of fludrocortisone acetate from tablets was 78 +/- 3%. The t(90) expressed with 95% confidence limits were 2 +/- 1 and 22 +/- 3 days for the solutions prepared from tablets and stored at +23 and +4 degrees C, respectively, whereas t(90) were 11 +/- 2 days and at least 60 days for the solutions prepared with the powder and stored at +23 and +4 degrees C, respectively. No color or odour changes were observed during the study period. The initial pH of the solutions prepared from tablets and powder were 7.7 and 6.9, respectively. No change of pH values was observed at the end of the 60 days. Significant degradation of fludrocortisone acetate occurred in formulations stored at +23 degrees C. Fludrocortisone acetate 40 microg/ml solutions prepared from tablets and powder were stable 19 days and at least 60 days, respectively, when stored at +4 degrees C. The solution prepared from powder is the best in term of stability and final concentration which is independent on the fludrocortisone acetate recovery.

[Drugs and drug abusers]. / Médicaments et abus toxicomaniaques.

DRUG ABUSERS: Drugs are widely used by toxicomaniacs to reproduce drug effects. Drug abusers generally start with psychotrops, but other abuse drug classes. Toxicomanic behavior leads to addictive practices that are difficult to control. BARBITURATES: Both the oral and intravenous routes are used. The expected result is a state of ecstasy with a feeling of comfort. Intoxication may cause respiratory depression. Barbiturates induce physical and psychic dependence. Abuse is not widespread with this class of drugs. BENZODIAZEPINES: Drug abuses widely use benzodiazepines orally or intravenously. They search for a flash effect, with sedation and a feeling of comfort. All benzodiazepines induce physical and psychic dependence. Death may result from combinations leading to respiratory depression. Flunitrazepam is the most widely abused benzodiazepine in France. It induces serious neuropsychic disorders. ANTIDEPRESSANTS: Few are used, mostly at high doses. OPIATES: Administration gives the same effect as heroine injection. Opiates induce physical and psychic dependence. The adverse effects are similar to those of morphine with a higher risk of respiratory depression. AMPHETAMINES: Few are used, either orally or intravenously. They induce a flash with excitation, euphoria, and a period of invincibility. This is followed by a period of depression with risk of suicide. Psychic dependence is high. ANTICHOLINERGIC ANTIPARKINSONIANS: These drugs are well known to abusers for their hallucinatory effect. They induce atropinic adverse effects and physical and psychic dependence. GAMMA-HYDROXYBUTYRATE: This anesthetic is used for its euphoria and sedation effects. It may induce falling sickness or coma, with a risk of respiratory depression. KETAMINE: Administered via the intranasal route, ketamine induces a state of indifference. Death has been observed. ANABOLIC AND ANDROGENIC STEROIDS: These drugs are used for their physical and psychic stimulating effect. They induce potentially dangerous adverse effects such as cardiovascular, hepatic, neurological and psychiatric disorders. Clinical signs of addiction and weaning are observed. OTHERS: Several other drug classes are used by abusers, including analgics, beta-adrenergic agents, nasal vasoconstrictors and corticosteroids.

[Drug interactions with methadone]. / Interactions médicamenteuses avec la méthadone.

PHARMACOKINETICS PHARMACODYNAMICS: Methadone is metabolized by cytochrome P450 enzymes in the liver microsomes and binds selectively to mu opiate receptors. Drugs metabolized by these enzymes or mu receptor competitors can modify the action of methadone. Genetic polymorphism influences plasma concentrations of the active levo enantiomer and thus clinical efficacy. ANTITUBERCULOSIS DRUGS: Rifampicin lowers methadome plasma levels so dose must be adapted. Rifabutin does not affect methadone kinetics. ANTI-EPILEPSY DRUGS: Phenytoin lowers blood levels of methadone by about 50% in 3 to 4 days. Other anti-epilepsy enzyme inducers (phenobarbital, carbamazepine) increase methadone metabolism. ANTI-VIRAL DRUGS: The area under the curve of plasma concentrations of zidovudine in presence of methadone increase by 43%, increasing the risk of undesirable effects. PSYCHOTROPES: Plasma levels of methadone increase by 20 to 100% in the presence of fluvoxamine. The benzodiazepine-methadone combination can be fatal due to respiratory depression. OTHER DRUGS: Brupenophine is a methadone agonist at the dose of 1 and 2 mg. Chronic alcoholism reduces the area under the curve while acute alcoholism increases it. Pure morphine agonists raise a major risk of respiratory depression while partial agonists favor the development of withdrawal symptoms.

Bethanechol chloride oral solutions: stability and use in infants.

OBJECTIVE: To assess the stability of a bethanechol chloride oral solution prepared from tablets. METHOD: The initial concentrations were determined. These solutions were stored at 4 degrees C for 90 days. During this period, the concentrations of the bethanechol chloride solutions were determined by spectrophotometry. The clinical efficacy of the oral solution was tested in five infants with gastroesophageal reflux disease by comparison of gastric pH before and after treatment. RESULTS: Significant decomposition of bethanechol chloride occurred in the two formulations. Bethanechol oral solution in sterile water for irrigation was well tolerated by five pediatric patients, and the clinical efficacy was equivalent to that of the tablet formulation. CONCLUSIONS: The bethanechol chloride oral solution 1 mg/mL in sterile water for irrigation was stable at least 30 days when stored at 4 degrees C and at an initial pH of 6.5. This formulation appears to be clinically acceptable and provides a convenient dosage form for use in pediatric patients.

Effect of ethanol on prostacyclin, thromboxane, and prostaglandin E production in human umbilical veins.

The purpose of this study was to determine the effects of ethanol on prostacyclin (PGI2), prostaglandin E (PGE), and thromboxane (TXA2) production in perfused human umbilical veins. PGI2, PGE, and TXA2 levels were measured from human umbilical veins perfused with either 25, 50, or 100 mM ethanol by radioimmunoassay of their stable metabolites. Alcohol content was measured by an enzymatic spectrophotometric assay. Data were analyzed by ANOVA and Fisher's Protected Least Significant Difference Test. Ethanol decreased PGI2 production in a concentration-dependent manner (p < 0.05). In a concentration of 25 mM, ethanol did not affect PGI2 production, whereas 50 mM decreased levels after 60 min of perfusion (p < 0.01). With 100 mM ethanol, PGI2 production was decreased after 15, 30, and 60 min of perfusion (ps < 0.05), and the TXA2/PGI2 ratio was significantly elevated at all time points (p < 0.01). Ethanol (100 mM) did not affect TXA2 or PGE production. Reduction of PGI2 levels and the increase in the TXA2/PGI2 ratio seen after ethanol perfusion in umbilical veins may cause vascular disruption in the umbilical-placental circulation. This may, in part, be a contributing mechanism to the teratogenic effects of ethanol.

Determination of cisapride and norcisapride in human plasma using high-performance liquid chromatography with ultraviolet detection.

A simple, rapid and reproducible high-performance liquid chromatographic assay for cisapride and norcisapride in human plasma is described. Samples of plasma (150 microl) were extracted using a C18 solid-phase cartridge. Regenerated tubes were eluted with 1.0 ml of methanol, dried, redissolved in 150 microl of methanol and injected. Chromatography was performed at room temperature by pumping acetonitrile-methanol-0.015 M phosphate buffer pH 2.2-2.3 (680:194:126, v/v/v) at 0.8 ml/min through a C18 reversed-phase column. Cisapride, norcisapride and internal standard were detected by absorbance at 276 nm and were eluted at 4.3, 5.3 and 8.1 min, respectively. Calibration plots in plasma were linear (r>0.998) from 10 to 150 ng/ml. Intraday precisions for cisapride and norcisapride were 3.3% and 5.4%, respectively. Interday precisions for cisapride and norcisapride were 9.6% and 9.0%, respectively. Drugs used which might be coadministered were tested for interference.