Biomedical subjects
Publications and source records attributed to R B Patel.
Computed tomography in a case of tuberculous psoas abscess is described. Additional information useful in planning surgical drainage was obtained by intraabscess contrast medium injection through a draining sinus.
Significant metastatic lesions of the osseous pelvis can be easily missed by conventional x-ray studies. Although the radionuclide bone scan is the method of choice for detection of metastatic lesions of the osseous pelvis, computed tomography should be used as a complementary study in certain patients.
The relative bioavailability of D-penicillamine was determined after single 500 mg oral doses of commercial tablets to healthy male volunteers under fasting and nonfasting conditions. In fasted individuals the mean maximum penicillamine level in plasma of 3.05 mcg/ml occurred at 3.8 h, and the area under the 0-12 h plasma curve was 14.7 mcg/h/ml. In nonfasted individuals the mean maximum penicillamine level of 1.52 mcg/ml occurred at 2.3 h, and the area under the 0-12 h plasma curve was reduced to 7.16 mcg/h/ml. Thus under these conditions food reduced systemic penicillamine availability by 1/2, but did not reduce the apparent absorption rate.
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Plasma levels of promethazine were determined using a high-pressure liquid chromatographic procedure incorporating a fixed wavelength (254 nm) UV detector, following single 50-mg intravenous, intramuscular, and oral doses to two male dogs. Initial plasma promethazine concentrations following intravenous doses were 556 and 535 ng/ml in the two dogs. The subsequent decline in drug levels were satisfactorily described by a triexponential function. Peak promethazine levels of 76 and 64 ng/ml were obtained 0.5 hr following intramuscular doses. Peak levels for the oral doses were 10.6 and 11.0 ng/ml occurring 2 hr after dosing. The apparent biological half-life of promethazine, obtained from only 2-3 data points, varied from 8.5 to 27.7 hr. Areas under the promethazine plasma curves, compared to values obtained from intravenous doses between 0 and 24 hr, indicated that systemic availability of intact drug was 55-73% following intramuscular injection and 8.3-9.5% following oral administration.
The relative bioavailability of tolazamide was determined, in healthy male volunteers, from four different tablet formulations manufactured by direct compaction or granulation processes and the results were compared with in vitro disintegration and dissolution values. Serum tolazamide levels were determined by a high-pressure liquid chromatographic method developed in this laboratory. Serum tolazamide levels from the formulation that gave rise to rapid absorption were described by one-compartment model kinetics with a mean absorption half-time of 1.0 hr and an elimination half-life of 4.6 hr. Peak serum levels occurred at 3.3 hr after drug administration. Marked differences were observed in drug bioavailability from the four tablets, and the mean cumulative relative fraction of dose absorbed was 1.0, 0.42, 0.75, and 0.91 from Formulations A, B, C, and D, respectively. The hypoglycemic effect was closely related to serum tolazamide levels. Disintegration times did not predict in vivo tolazamide bioavailability. Dissolution rates provided an approximate rank order correlation with in vivo absorption but failed to be predictive among formulations. Currently available in vitro tests do not accurately predict tolazamide in vivo bioavailability characteristics among different formulations and manufacturing processes but may be useful to ensure lot-to-lot uniformity in bioavailability for a given formulation and specific method of manufacture.
The corresponding concentrations of rosoxacin in serum (S) and prostatic tissue (PT) were determined in 15 patients undergoing transurethral resection of the prostate because of benign prostatic hyperplasia. Rosoxacin concentrations were determined employing both bioassay and a high-pressure liquid chromatography procedure, with excellent correlation between the two methods. Two dosage schedules were followed, resulting in median serum concentrations of 3.6 and 5.8 microgram/ml, respectively. The ratio of PT/S was found to be fairly constant and surprisingly high, the median values being 0.46 and 0.56. These results indicate that concentrations of rosoxacin are obtained in prostatic interstitial fluid in the range of the minimal inhibitory concentrations for most of the gram-negative pathogens causing bacterial prostatitis and urinary tract infections. Acceptable drug concentrations also were determined in urine and cerebrospinal fluid. The results obtained in this study warrant further clinical trials for rosoxacin in the treatment of bacterial prostatitis and urinary infections.
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Computed tomography (CT) was used for study of the osseous pelvis in 43 patients with definitive pathological or clinical follow-up. CT accurately characterized and determined extent of bone and soft-tissue involvement; neoplasms and other disease processes, such as sacroiliac joint disease, were well localized. In cases of trauma, CT was able to identify, localize, and characterize fracture fragments and bone or joint displacement. CT was judged "useful" or "definitive" in 80% of all lesions and 96% of neoplasms studied.
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The bioavailability of chlorothiazide was examined following single oral solution doses to eight healthy male volunteers. Drug was administered in 250 ml of water after overnight fast. Bioavailability was determined by measuring 72 h urinary recovery of unchanged drug. Mean urinary recovery from 50, 100, and 250 mg doses was, respectively, 28.3, 47.0 and 83.3 mg, representing 56.4, 47.0, and 33.3 per cent of the administered dose. The correlation coefficient between dose size and percentage recovery was -0.662. These results add support to previous suggestions that the absorption of chlorothiazide from the gastrointestinal tract is saturable, and that the availability of chlorothiazide may be similar to that of hydrochlorothiazide when these compounds are administered in the same dosage range.
The bioavailability and pharmacokinetics of two hydrochlorothiazide products were compared following single 50 mg oral doses to 20 healthy male volunteers. Plasma and urine were assayed for hydrochlorothiazide by a specific and sensitive HPLC method. Plasma profiles of hydrochlorothiazide were adequately described by a triexponential function. The bioavailability of hydrochlorothiazide from the two brands did not differ significantly as judged by the values of Cmax, tmax, AUC0 leads to infinity, mean residence time, variance of residence time, and urinary excretion of unchanged drug. Close similarity was observed between urinary excretion rates and concentrations of drug in plasma.
The influence of prior food ingestion, and also of varying fluid volumes, on plasma theophylline levels was examined following single oral doses of two sustained-release formulations, Theobid (260 mg) and Theo-Dur (200 mg) and one partially enteric-coated formulation, Choledyl (128 mg), to 9 healthy volunteers. Prior food ingestion tended to delay the absorption of theophylline from all formulations to a small extent. This effect was observed only at early sampling times, and plasma drug profiles were similar for all treatments within a particular formulation. Theobid and Theo-Dur gave rise to plasma profiles that were characteristic of sustained-release formulations, with mean Cmax values of 5.5-5.7 micrograms ml-1 (Theobid) and 2.8-3.2 micrograms ml-1 (Theo-Dur) occurring at 5.8-9.1 h after dosing. Choledyl gave rise to a longer absorption lag time than the other formulations but was subsequently absorbed at a faster rate yielding mean Cmax values of 3.2-3.5 micrograms ml-1 at 2.8-4.1 h. The intersubject variability in theophylline plasma levels, and also in most pharmacokinetic parameter values, was generally less following Theo-Dur compared to the other formulations.