Stability of imipenem and cilastatin sodium in total parenteral nutrient solution.

The chemical stability and compatibility of imipenem-cilastatin sodium (Primaxin) in two different total parenteral nutrient (TPN) solutions was determined. TPN solutions consisted of 4.25% and 5% amino acids with 25% and 35% dextrose, respectively. Imipenem-cilastatin sodium was constituted with 10 ml of sterile water and admixed with 90 ml of TPN solution for a final concentration of 5 mg/ml of each drug. The final solutions were assayed at times 0 (immediately after admixture), 15 min, 30 min, 1, 4, 8, and 24 hr by a stability-indicating high-performance liquid chromatographic assay. Concurrently, test TPN solutions were monitored for pH changes, color changes, and precipitate formation. The potential effect of imipenem-cilastatin sodium on the stability of amino acids and other TPN additives was not evaluated. Imipenem and cilastatin sodium was stable (greater than or equal to 90% recovered) in each TPN solution at 15 min. A significant (greater than or equal to 10%) and steady decrease of imipenem recovery occurred at subsequent sampling times. Cilastatin appeared more stable than imipenem in both TPN solutions. A physical color change from colorless to dark orange appeared in each TPN solution over the 24-hr study period. Imipenem-cilastatin sodium is stable for 15 min in the TPN solutions studied; however, until the stability of the amino acids can be determined, the antibiotic should be administered through a separate line or Y-site while the TPN infusion is interrupted.

[Study of the in vivo penetration of cotrimoxazole in alveolar macrophages]. / Etude de la pénétration in vivo du cotrimoxazole dans les macrophages alvéolaires.

Kinetic of cotrimoxazole was studied in serum, alveolar macrophages and BAL fluid from guinea pigs receiving sulfamethoxazole (SMX, 100 mg/kg) and trimethoprim (TMP, 20 mg/kg). Guinea pigs were killed by cervical dislocation 30 min, 1 h, 3 h, 6 h and 24 h after intraperitoneal injection. Lung lavage was performed to obtain alveolar macrophages and BAL fluid. TMP and SMX levels were assayed using high-performance-liquid chromatography. Highest SMX levels were obtained in serum at 30 min, in BAL fluid at 1 h and in alveolar macrophages at 3 h. Mean SMX/TMP ratios (30 min, 1 h, 3 h) was 26.5 +/- 0.8 in serum, 3.76 +/- 1.8 in BAL fluid and 1.15 +/- 0.02 in alveolar macrophages.

Improvement in potency assay of measles-mumps-rubella trivalent vaccine: interference between components and measures for its elimination.

In the potency assay of trivalent measles-mumps-rubella (MMR) vaccine by the immunocytochemical focus assay reported previously (Fukuda et al., 1987), development of rubella foci in RK13 cells was inhibited in the presence of a large excess of mumps component, resulting in an underestimation of the titre of the rubella component. When RK13 cells are infected with the mixture of mumps and rubella viruses, mumps virus interfered with the growth of rubella virus. Interference was mediated most likely by interferon induced by mumps virus. The interference was eliminated by a partial neutralization of mumps component by the addition of anti-mumps serum to the inoculum to RK13 cells. Improved method of potency assay of MMR vaccine incorporating the above measures and other modifications are described.

Plasma concentrations and analgesic effect of EMLA (lidocaine/prilocaine) cream for the cleansing of leg ulcers.

Plasma concentrations of lidocaine and prilocaine were assessed in 8 patients after the application of 8-10 g EMLA 2% cream for 60 min to leg ulcers measuring 31-80 cm2. Maximum individual plasma concentrations were 205 ng/ml for lidocaine and 79 ng/ml for prilocaine, which is twenty times lower than those associated with toxicity. The analgesic effect of EMLA 2% and 5% cream for the surgical cleansing of leg ulcers was compared in a double-blind, four-period, cross-over study in 10 patients. The ulcer was covered with a thick layer of cream for 30 min before four consecutive debridements 1-4 days apart. While the 2% and 5% creams had similar analgesic effects post-cleansing pain tended to be more frequent with the 2% cream.

Plasma concentrations of sulfadoxine-pyrimethamine and of mefloquine during regular long term malaria prophylaxis.

The plasma concentrations of sulfadoxine, pyrimethamine, mefloquine and its major metabolite were determined in 18 healthy male volunteers who had regularly taken either 500 mg of sulfadoxine and 25 mg of pyrimethamine (Fansidar) weekly or 250 mg mefloquine regularly every 14 d during 6 months for malaria prophylaxis. The mean trough concentrations of sulfadoxine, pyrimethamine and mefloquine were 194, 0.28 and 1.48 mumol/litre and the mean half lives were 7.7, 4.2 and 25 d respectively. The variation in area under the curve for the 3 drugs was only 2-3 fold. The findings do not indicate that drug accumulation or induction of metabolism occurred during long-term usage.

Suicide by ingestion of T-61.

T-61 is an agent used for euthanasia of animals and is primarily administered by iv injection. When so used it rapidly induces deep anesthesia and cerebral death. We report our findings in a case of ingestion of T-61 with suicidal intent. The coroner's report stated that the individual survived for 20 to 30 min and that death was due to cardio-respiratory failure. Levels of embutramide in the blood and liver are comparable to those reported in a number of animal species following the traditional routes of administration.

Derivative spectrophotometric determination of clotrimazole in single formulations and in combination with other drugs.

First (D1) and second (D2) derivative spectrophotometric methods are presented for the determination of clotrimazole after its acid hydrolysis. Mixtures of clotrimazole with azidamfenicol and dexamethasone have been assayed using D2 measurement at 302 nm after acid hydrolysis for clotrimazole, D1 measurement at 288 nm for azidamfenicol, and D1 measurement at 436 nm after reaction with phenylhydrazinium sulfate for dexamethasone. Reproducible results with relative standard deviations of less than 2% are obtained. The proposed method has been successfully applied to the analysis of creams, topical solutions, and vaginal tablets.

[Spectrodensitometric determination of lidocaine-chloride in antihemorrhoidal agents]. / Spektrodenzitometrijsko odredivanje lidokain-hlorida u nekim antihemoroidalijama.

Spectrodensitometric method was used in determination of lidocaine-chloride in some antihemorrhoidal agents after thermomicrodetection and its direct thin layer coating. This procedure is based on transference of the studied substance into the gaseous state, its quantitative transference on the basic layer of silicagel GF254, isolation in the benzene-methanol mixture and its identification. Determination was performed by spectrodensitometric determination of absorption. The results obtained are precise and reproducible and the procedure is suitable for determination of lidocaine-chloride in micrograms.

Stability of concentrated trimethoprim-sulfamethoxazole admixtures.

The stability of trimethoprim-sulfamethoxazole (TMP-SMX) at various concentrations in 5% dextrose injection or 0.9% sodium chloride injection was studied. Appropriate volumes of TMP-SMX formulation (80 mg TMP and 400 mg SMX/5 mL) were mixed with 5% dextrose injection or 0.9% sodium chloride injection to provide dilutions of 1:25 v/v, 1:20 v/v, 1:15 v/v, and 1:10 v/v. Aliquots were removed at 0, 0.5, 1, 2, 4, 8, 14, 24, and 48 hours and filtered. The pH of the samples was determined, and the samples were assayed for trimethoprim and sulfamethoxazole content by high-performance liquid chromatography. Admixtures were visually inspected for precipitate before each sample was removed. The concentration of SMX in all admixtures did not change during the study period. The stability of TMP was dependent on concentration and vehicle. At a 1:25 v/v dilution, TMP was stable for 48 hours in 5% dextrose injection and 0.9% sodium chloride injection. At a 1:20 v/v dilution, TMP was stable for 24 hours in 5% dextrose injection and 14 hours in 0.9% sodium chloride injection. At a 1:15 v/v dilution, TMP was stable for four hours in 5% dextrose injection and two hours in 0.9% sodium chloride injection. At a 1:10 v/v dilution, TMP was stable for one hour in 5% dextrose injection and 0.9% sodium chloride injection. Concentrated solutions of TMP-SMX should be prepared in 5% dextrose injection, infused within one hour of preparation, and visually inspected for precipitation before and during infusion.

[Identification of tanshinones with related compounds by high performance thin layer chromatography and mass spectrometric analysis].

28 compounds isolated from Danshen (Salvia miltiorrhiza Bunge and S. przewalskii Maxium) were identified by both HPTLC and mass spectrometric analysis. The mass spectra of tanshinones and related terpenoids have been examined and a number of characteristic features noted which might be helpful in the identification of these compounds. The Rf values of five groups of tanshinones and related compounds in six solvent systems were given. They can be used for identifying several epimeric compounds which are difficult to identify by mass spectra alone.

[P-matrix spectrophotometric determination of 6 components contained in compound reserpine tablets].

P-matrix method has been developed for the simultaneous determination of vitamin B1, vitamin B6, chlordiazepoxide, dihydralazins sulfate, promethazine hydrochloride and hydrochlorothiazide contained in compound reserpine tablets consisting of 10 components. The optimal wave-length for measurement was successfully selected based on the principle of condition number. The influence of experimental error, number of wavelength and condition number deviation of component concentration from formula were discussed. The average recoveries varied from 97-103% with CV less than or equal to 9.5% (n = 11).

[Analysis of 5-pyrazolinone derivatives in pharmaceutical products. I. Spectrophotometric analysis of two-component drugs containing propyphenazone]. / Oznaczanie pochodnych 5-pirazolinonu w preparatach farmaceutycznych. I. Spektrofotometryczne oznaczanie leków dwuskladnikowych z propyfenazonem.

Two new methods for the determination of active components in the preparations Gardan P (propyphenazone + noramidopyrine) and Pabialgin P (propyphenazone + allobarbital) have been elaborated. The first one is a direct spectrophotometric method based on measurements of absorption at two wave lengths; at lambda = 218 and 270 nm for Pabialgin P, and at lambda = 232 and 260 nm for Gardan P. The second method, the chromatographic-spectrophotometric method has been based on separation of individual components by thin-layer chromatography followed by their spectrophotometric determination. The results obtained by the above two methods were compared with the results given by the titrimetric method according to the producer's standard. Statistic analysis by the Student's and F-Snecodor's tests has shown that all these methods are equally precise but differ in accuracy, sensitivity and selectivity. The spectrophotometric determination of allobarbital has proved to show the highest accuracy (Wz = 1.4), while the acidimetric determination of propyphenazone in the non-aqueous medium has appeared least accurate (Wz = 3.7). Sensitivity of the tested methods was found to range from 3 x 10(-4) g/cm3 for the titrimetric methods to 6 x 10(-6) g/cm3 for direct spectrophotometric measurements. In respect of selectivity, only the chromatographic-spectrophotometric method has proved to be enough selective and to give quite correct results.

Determination of embutramide in mammalian tissues.

T-61 is a commonly used euthanasic agent containing N-[2-[m-methoxyphenyl)-2-ethyl-buty1(1)]-gamma-hydroxybutyramid e (embutramide), 4,4'methylenebis(cyclohexyl-trimethylammonium iodide), and tetracaine hydrochloride. In order to confirm the exposure of animals and man to T-61, a procedure was developed for identification and quantification of embutramide in tissues and body fluids. Tissue was homogenized in acetonitrile (CH3CN) and the drug partitioned into methylene chloride (CH2Cl2) from aqueous CH3CN at neutral pH and at pH 9. The drug was purified by gel permeation chromatography in cyclohexane/CH2Cl2 (85:15). Embutramide was identified by gas chromatography-mass spectrometry on a 0.25 mm x 15 m fused silica capillary column of 0.25 micron DB-5, programmed from 215 to 275 degrees C at 25 degrees/min with El ionization at 70 ev. Quantification was selected ion monitoring of m/z 135, 190 and 293. Embutramide was examined in brain, lung, liver, kidney, skeletal muscle, urine, bile, eye fluid and blood of bovine, canine, caprine, feline, ovine and porcine species.

Pharmacodynamic evaluation of ofloxacin and trimethoprim-sulfamethoxazole in vaginal fluid of women treated for acute cystitis.

Vaginal colonization with Escherichia coli is an integral step in the development of acute cystitis, and persistent vaginal coliform colonization may also be a predisposing step to recurrent urinary tract infections. For this reason, we evaluated antibiotic concentrations in the vaginal fluid, serum, and urine and the vaginal colonization by E. coli of 56 women receiving either ofloxacin (200 mg orally twice a day) or trimethoprim-sulfamethoxazole (TMP-SMX) (160/800 mg orally twice a day) for the treatment of acute cystitis. Ofloxacin and trimethoprim both penetrated into vaginal fluid to a considerably greater extent than sulfamethoxazole. Among 33 patients given ofloxacin, the concentration of the drug in vaginal fluid during one dosage interval ranged from 1.6 to 21.6 micrograms/ml. In 21 women given TMP-SMX the range of drug concentrations in vaginal fluid was 2.6 to 32.5 micrograms/ml for TMP and 1.0 to 6.2 micrograms/ml for SMX. Treatment with both ofloxacin and TMP-SMX remarkably reduced vaginal colonization by E. coli during and up to 30 days after therapy. For the ofloxacin-treated women, eradication of vaginal E. coli was associated with a high ratio of drug concentration in vaginal fluid to that in serum. We conclude that ofloxacin and TMP both achieve high concentrations in vaginal fluid and are equally successful in eradicating E. coli from the vagina.

[The action of gamma irradiation on terrilytin immobilized on cellulose-fiber materials]. / Deistvie gamma-oblucheniia na terrilitin, immobilizovannyi na tselliuloznykh voloknistnykh materialakh.

The effect of gamma-radiation on terrilytin, a proteolytic enzyme immobilized on modified and nonmodified cellulose materials was studied by EPR. Dialdehyde cellulose and graft copolymer of cellulose and polyacrylic acid were used as the modified cellulose materials. Dependence of the native and immobilized terrilytin activity and the content of free radicals in the irradiated samples on the irradiation dose was observed. It was shown that immobilization of the enzyme led to increasing of its stability to the effect of the ionizing radiation. This was due to transfer of the free valency from terrilytin to the carrying polymer which prevented radiation and chemical destruction of the enzyme. The proteolytic activity of native terrilytin subjected to gamma-irradiation markedly decreased because of intramolecular and intermolecular interactions during reactions of the terrilytin free radicals, since in this case there was no polymer as an acceptor of the enzyme free valency.