International interlaboratory quality control program for measurement of antiretroviral drugs in plasma.

An international interlaboratory quality control program for measurement of antiretroviral drugs was initiated. The first round was confined to protease inhibitors and showed large variability in the performance of participating laboratories. The results demonstrate the need for and utility of an ongoing quality control program in this area of bioanalysis.

Determination of nevirapine, an HIV-1 non-nucleoside reverse transcriptase inhibitor, in human plasma by reversed-phase high-performance liquid chromatography.

A sensitive and rapid high-performance liquid chromatography method has been developed to measure the levels of the HIV-1 non-nucleoside reverse transcriptase inhibitor nevirapine in human plasma. The sample pre-treatment consists of a protein precipitation with perchloric acid. A Hypersil ODS column is used at ambient temperature and a wavelength of 280 nm is used for ultraviolet detection.

Stability of dithranol in creams.

The stability of the anthrachinone derivative dithranol in creams was studied during storage at temperatures of 4 degrees C and 20 degrees C. Aluminum-coated tubes with 0.1, 0.

Long-term stability of morphine and bupivacaine mixture for spinal use.

From clinical studies it has been proven that morphine in combination with bupivacaine is applicable in cancer pain. The availability of a ready to use parental dosage form of morphine and bupivacaine is comfortable for health care workers. Stability of a morphine or a bupivacaine preparation or a combination of both in a PVC cassette or polypropylene syringe for spinal use is examined in several studies.

Simultaneous determination of the HIV-protease inhibitors indinavir, nelfinavir, saquinavir and ritonavir in human plasma by reversed-phase high-performance liquid chromatography.

A sensitive high-performance liquid chromatographic method has been developed for the simultaneous determination of the four licensed HIV-protease inhibitors indinavir, nelfinavir, saquinavir and ritonavir. An aliquot of 500 microl plasma, spiked with internal standard, was extracted with 0.5 ml 0.

Safety of lidocaine-prilocaine cream application four times a day in premature neonates: a pilot study.

Unlabelled: Although safety is established for lidocaine-prilocaine cream application to the heel once a day in neonates, it is often necessary to repeat heel lances several times a day in the clinical situation. A pilot safety study applying 0.5 g lidocaine-prilocaine cream to the heel covering an area of 5 cm2 with an occlusive dressing during 30 min four times a day was carried out.

Skin irritation by dithranol cream. A blind study to assess the role of the cream formulation.

In connection with a national cost-effective evaluation study of short contact dithranol therapy for psoriasis, the question arose whether dithranol cream irritation is influenced by constituents of the vehicle. To establish the role of the different components of the vehicle in the mechanism of dithranol irritation, the dithranol 3% cream used in the evaluation study and its vehicle with nine different combinations of its components were tested in a blind study. The creams were applied for 15, 30 and 45 min on the backs of 12 healthy volunteers.

Determination of indinavir, an HIV-protease inhibitor, in human plasma by reversed-phase high-performance liquid chromatography.

A sensitive high-perforrmance liquid chromatographic assay has been developed to determine the concentrations of the HIV-protease inhibitor indinavir in human plasma. The sample pretreatment involved a protein precipitation procedure using 100 microl of human plasma and 400 microl of acetonitrile. Chromatography was carried out on an Octadecyl column using a mobile phase of acetonitrile-water (40:60, v/v).

Chiral cognisance: a road to safer and more effective medicinal products.

A quarter of all synthetic medicinal drugs contain a mixture of equal proportions of two molecules that have the same chemical constitution but differ in the spatial arrangement of their constituent atoms such that each is a mirror-image of the other, like the right and left hand. Biologically, receptors which are stereospecific react with only one of the two components of the mixture to produce the desired therapeutic effect, while the other is inactive or may interact with different receptors to cause undesirable, even toxic, effects. Development of syntheses that produce a preponderance of the required form, and efficient separation of mixtures, will result in safer and more effective medicinal products.

Interindividual variation in the capacity-limited renal glucuronidation of probenecid by humans.

A dose of 1,000 mg probenecid was administered orally to 14 human volunteers in order to quantify the maximal rate of formation and excretion of probenecid acyl glucuronide in the urine. Probenecid showed dose-dependent pharmacokinetics. Plasma protein binding of probenecid was high, being somewhat higher in males (90.

Capacity-limited renal glucuronidation of probenecid by humans. A pilot Vmax-finding study.

Probenecid shows dose-dependent pharmacokinetics. When in one volunteer the dose is increased from 250 to 1,500 mg orally, the t1/2 increased from 3 to 6 h. The Cmax was 14 micrograms/ml with a dosage of 250 mg, 31 micrograms/ml with 500 mg, 70 micrograms/ml with 1,000 mg and 120 micrograms/ml with 1,500 mg.

Direct high pressure liquid chromatographic analysis and preliminary pharmacokinetics of enantiomers of oxazepam and temazepam with their corresponding glucuronide conjugates.

Three high pressure liquid chromatographic systems for the separation of oxazepam, temazepam and their glucuronides (system A), the separation of their R,S glucuronide diastereomers (system B) and the chiral separation of the parent drugs (system C) are described. Preliminary pharmacokinetics of R,S-oxazepam and R,S-temazepam in a human volunteer reveal that the protein binding of the glucuronides is lower than that of the parent drugs, but that there is no difference in protein binding between the R-oxazepam/temazepam and S-oxazepam/temazepam and their corresponding glucuronides. The S-glucuronide is the main metabolite formed and excreted by man.

HPLC analysis and pharmacokinetics of the enantiomers of R,S-oxazepam and R,S-temazepam with their corresponding glucuronide conjugates in urine and plasma of man.

R,S-Oxazepam and R,S-temazepam can be separated in their enantiomers by means of a chiral AGP column. The corresponding R- and S-glucuronide conjugates can be separated on a normal reversed-phase C18 column. Man conjugates the S-enantiomer of oxazepam and temazepam both better than the R-enantiomer.

Pharmacokinetics of baclofen in spastic patients receiving multiple oral doses.

The pharmacokinetics of racemic baclofen as determined from plasma and urine data in six spastic patients treated with individualized oral doses, 30-80 mg daily, are presented. Peak plasma concentrations were achieved 1.9 h (+/- 0.

Pharmacokinetics of intravenously administered dantrolene and its 5-hydroxy metabolite in dogs.

Dantrolene, a direct acting muscle relaxant used orally for spasticity, has appeared to be effective in the prevention and treatment of malignant hyperthermia in man and animals when administered intravenously. Its pharmacokinetics following intravenous administration have been studied in dogs. Concentrations of dantrolene and its metabolites in plasma, urine, and bile were determined by high-performance liquid chromatography.

Plasma and urinary excretion kinetics of oral baclofen in healthy subjects.

Baclofen, a centrally acting muscle relaxant, is used in the treatment of spasticity. Its pharmacokinetics has been derived from plasma and urine data in four healthy subjects, whose renal function was simultaneously measured. After oral administration of a single 40 mg dose, baclofen was mainly excreted unchanged by the kidney, 69 (14)%.

Comparison of the pharmacokinetics of intravenously administered rac-baclofen and its (-)-(R)- and (+)-(S)-enantiomers in dogs.

Baclofen is a centrally acting muscle relaxant marketed as the racemate. Since only the (-)-(R)-enantiomer is pharmacologically active, the pharmacokinetics of rac-baclofen and its enantiomers were studied individually in the same group of dogs to determine if there was any stereospecificity in the drug's kinetics after a single intravenous dose. High-pressure liquid chromatography was used to determine concentrations in plasma and urine.