ABSTRACT
Oral doses of misonidazole between 0.75 and 1.3 g/m2 were administered during 3-5 days per week to 21 patients with various malignancies. Mean plasma levels of misonidazole and desmethylmisonidazole at the times of radiotherapy were in the range 20-50 and 2-12 mg/l respectively. Slight accumulation of misonidazole and desmethylmisonidazole in plasma was observed with a dosage interval of 24 h. In patients with anticonvulsant comedication plasma elimination half-lives of misonidazole of 4.1-8.9 h were found. Observed side-effects were nausea and vomiting (9%), exanthema or rashes (14%) and mild peripheral neuropathy (9%).
Subject(s)
Misonidazole/metabolism , Neoplasms/radiotherapy , Nitroimidazoles/metabolism , Adult , Aged , Female , Half-Life , Humans , Kinetics , Male , Middle Aged , Misonidazole/adverse effects , Misonidazole/analogs & derivatives , Misonidazole/blood , Misonidazole/therapeutic use , Neoplasms/metabolism , Nitroimidazoles/bloodABSTRACT
A reversed-phase high-performance liquid chromatographic method with reductive mode electrochemical detection was developed for the determination of misonidazole and desmethylmisonidazole in plasma. A thin-layer amperometric detector with glassy carbon working electrode was used to detect the nitroimidazoles at a potential of -0.60 V. The calibration curves were linear. The within-day and day-to-day coefficients of variation were below 3% for plasma misonidazole concentrations of 6-60 mg/l and 1-15 mg/l for desmethylmisonidazole. Electrochemical detection limits were between 2 and 4 pg, which is about 10-20 times lower than that obtained by detection at 323 nm. Limits of quantitation of the nitroimidazoles in plasma were in the order of 1-2 micrograms/l. Under the described conditions other nitroimidazoles and nitro compounds can also be detected with ultimate sensitivity by reductive mode electrochemical detection.
Subject(s)
Misonidazole/blood , Nitroimidazoles/blood , Chromatography, High Pressure Liquid/methods , Electrochemistry , Humans , Misonidazole/analogs & derivatives , Nitro Compounds/analysis , Spectrophotometry, UltravioletABSTRACT
Plasma concentration and pharmacokinetic data of a sustained-release theophylline (Theolair retard) was compared with that of a short-acting theophylline (Theolair) in six normals and six patients with asthmatic bronchitis. Steady-state plasma levels were reached on day 4 or earlier for both Theolair retard and Theolair. Theolair retard showed stable plasma concentrations. Patients showed lower (maximal) values for the plasma levels for Theolair retard and for Theolair and a shorter elimination half-life time for Theolair. This may perhaps be explained by the larger number of smokers among the patients versus the normals. As for the large interindividual variation in plasma levels and pharmacokinetics it seems advisable to administer theophylline guided by plasma levels estimated on the 4th day of administration, about 3 h after the morning dose.
Subject(s)
Asthma/metabolism , Theophylline/metabolism , Adult , Delayed-Action Preparations , Humans , Kinetics , Middle Aged , Theophylline/administration & dosageABSTRACT
A high-performance liquid chromatographic method for the simultaneous determination of misonidazole and desmethylmisonidazole in plasma is described. After plasma is deproteinized with methanol and the diluted supernatant is chromatographed on a C18 reversed-phase column, both compounds are quantitated by means of an internal standard. The coefficients of variation of within-day and day-to-day precision are below 5.0% for misonidazole in the concentration range of 25-250 mg/l and below 6.1% for desmethylmisonidazole in the concentration range of 2.5-25.0 mg/l. Calibration curves are linear and an analytical recovery varying from 97.6 to 99.8% is obtained. The detection limits for misonidazole and desmethylmisonidazole in plasma are 1.4 mg/l and 0.7 mg/l, respectively.
