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Biomedical subjects

D S Sitar

Publications and source records attributed to D S Sitar.

140 records · Page 8Linked to original sources
PubMed1975

Plasma theophylline concentrations measured by high-pressure liquid chromatography.

We present a specific, sensitive high-pressure liquid-chromatographic assay for theophylline in plasma. Only 0.5 ml of plasma is required for each determination, and the lower limit of detection by this method is 0.1 mg/liter. Other xanthines and their metabolites do not interfere. This method is suitable for use in studying the pharmacokinetics of this drug in infants and children, from whom only small volumes of blood are available.

Aminophylline↗
PubMedDate not supplied

Disposition of 5-fluorouracil during chronic hepatic arterial infusion to patients with carcinoma in the liver and effect on circulating platelets.

5-Fluorouracil was administered by continuous hepatic intra-arterial infusion to eight patients with the diagnosis of cancer of the gastrointestinal tract and hepatic metastases. Its elimination characteristics were investigated to see if they correlated with therapeutic effect or reduced clinical toxicity when the drug was given by this route. Urinary excretion of drug and metabolites was similar to findings after intravenous bolus doses. Disposition changes could not be correlated with therapeutic effect or clinical toxicity. A dose-related biphasic effect of 5-fluorouracil was found on circulating platelets. Doses greater than 6 mg kg-1 d-1 decreased the number of circulating platelets, while doses less than that resulted in an increase in circulating platelets. Further studies are required to determine the mechanism of the effect of 5-fluorouracil on platelets.

Adult↗
PubMedDate not supplied

Acetylsalicylic acid metabolites in blood and urine after plain and enteric-coated tablets.

Acetylsalicylic acid (ASA) was administered orally as a single dose to 7 healthy male volunteers as plain or enteric-coated (Entrophen) tablets using a crossover design. Blood and urine samples were collected and analysed for ASA metabolites by high performance liquid chromatography. Labile and stable glucuronide conjugates of salicylic acid (SA) were measured in urine after differential hydrolysis with glucuronidase. Plasma kinetic parameters for the ASA metabolites SA and salicyluric acid were not different for the 2 formulations, apart from the delayed appearance after the enteric-coated tablets. Total urinary recovery, and recovery of salicyluric acid and the two SA glucuronides were not different, thus confirming the equivalent bioavailability and metabolite profile of the 2 ASA formulations.

Adult↗
PubMedDate not supplied

Slow release theophylline disposition and effect in elderly patients with chronic obstructive lung disease: influence of dose formulation and institutionalization.

We studied the steady-state disposition of slow release theophylline tablets and granules in 12 institutionalized (I) and 12 community-dwelling (C) elderly patients with fixed chronic obstructive lung disease. Design was open label with random order crossover; each formulation was given 5 min before food every 12 h for 7 days. Age (median 70 y, range 55-88), sex, smoking status, and baseline lung function off drug were similar. Though plasma concentration (Cp) was higher with the tablets as was the area under the Cp vs time curve: 134 (74-252) vs 121 (75-197) mg h l-1; p = 0.028. The standard deviation of Cp over one dose interval was lower with the granules. FEV 1.0 was slightly improved over baseline. Dose required to reach target Cp was higher in the institutionalized group (12.6 vs 8.6 mg kg-1 day-1; p = 0.003) as was apparent clearance; I:94 (43-148) ml hr-1 kg-1 vs C:68 (34-163); p = 0.003. Although bioavailability was slightly reduced for the granules, fluctuations of Cp was less, and we failed to find a food effect that was clinically important in geriatric subjects.

Aged↗
PubMedDate not supplied

Amantadine acetylation may be effected by acetyltransferases other than NAT1 or NAT2.

Amantadine is a drug with a primary amino group, and consequently a likely candidate for metabolism by acetylation. This study assessed the possibility that a person's polymorphic (NAT2) acetylator phenotype could be used to predict the extent of amantadine acetylation. Thirty-eight normal, healthy volunteers were NAT2 acetylator phenotyped with sulfapyridine. Of the six fastest (75-86%) and six slowest (34-40%) sulfapyridine acetylators, two and three, respectively, had acetylamantadine present (18-338 microg) in the 8-h urine collection. There was no correlation between NAT2 acetylator phenotype and amantadine acetylation (p<0.5), and no difference in the total urine amantadine excreted over 8 h between acetylators and nonacetylators (28.3+/-9.7 vs. 30.4+/-9.6 mg, respectively, mean +/- SD). Acetylamantadine represented 0.1-1.5% (median 0.5%) of urinary drug content over 8 h. Our data confirm that amantadine is acetylated in humans and demonstrate for the first time that the extent is not correlated with NAT2 acetylator phenotype. Parallel in vitro enzyme studies indicate the possibility that neither NATI nor NAT2 is responsible for acetylation of amantadine.

Acetylation↗
PubMedDate not supplied

'Pseudo' treatment failure of pulmonary tuberculosis in association with a tuberculoma.

Failure of tuberculosis patients to respond to treatment is usually explained by one or more of five mechanisms: improper drug prescription; patient nonadherence to prescribed therapy; primary or acquired drug resistance; drug malabsorption; and rarely, exogenous reinfection with a drug-resistant isolate. Response to treatment is best measured bacteriologically; two different smear and one culture criteria for failure are widely used. Patients meeting either smear, but not culture, criteria for treatment failure may be said to have 'pseudo' treatment failure. Whether a patient can meet both smear criteria for failure, and not have a mechanism for treatment failure nor meet culture criteria, is unknown. A case of 'pseudo' treatment failure is reported in which both smear criteria for failure were met, but no mechanism for failure was proven to be operative.

Antitubercular Agents↗
PubMedDate not supplied

Diazoxide concentration-response relation in hypertension.

The pharmacokinetic disposition and antihypertensive response of bolus infusions of diazoxide, 1, 2, or 4 mg/kg over 5, 10, or 20 seconds, were examined in seven patients with chronic stable essential hypertension and mean arterial pressures (MAP) between 122 and 155 mm Hg off therapy. Maximal reductions in MAP were noted 2 minutes after each dose, and a linear correlation was obtained in all patients between dose or plasma diazoxide concentration and maximal change in MAP. Individual concentration-time curves were analyzed to determine the apparent volume of distribution at steady state (Vdss range, 0.178 to 0.250 liter/kg), beta t 1/2 (range, 32 to 62.5 hours), and plasma clearance rate (Clp range, 2.2 to 5.3 ml/kg . hour-1) for the calculation of loading and maintenance doses designed to produce steady-state concentrations within 0.5 hours. These infusions resulted in steady-state reductions in MAP (16% to 30%) which could be predicted from the concentration-response curves of each patient after bolus infusions. With the use of kinetic principles, a diazoxide dose regimen (average load, 7.5 mg/kg at 7.5 mg/min; average maintenance, 10% of loading dose every 6 hours) produced gradual and predictable reductions in MAP in patients with accelerated hypertension, since the response was proportional to plasma diazoxide concentrations.

Adolescent↗
PubMedDate not supplied

Pill count, self-report, and pharmacy claims data to measure medication adherence in the elderly.

OBJECTIVE: To compare medication adherence calculated from four different data sources including a pill count and self-report obtained during a home medication history, as well as calculations based on refill frequency derived from a provincial prescription claims database (manual and electronic). DESIGN: Baseline medication adherence was collected as part of a prospective, randomized, controlled study. Mean medication adherence results obtained from the four data sources were compared using repeated-measures ANOVA followed by a Tukey's multiple range test. SETTING: A pharmacy consultation service located at an interdisciplinary wellness center for noninstitutionalized elderly. PATIENTS: 65 years or older, noninstitutionalized, taking one or more prescribed or nonprescribed medications. Clients would either present to the wellness center or be referred by the Provincial Home Care program. RESULTS: When calculated from self-report or manual or electronic prescription claims data, mean percent adherence by drug was high and not statistically different (95.8% +/- 17.1%, 107.6% +/- 40.3%, and 94.6% +/- 24.0%, respectively), whereas the pill count adherence was significantly lower at 74.0% +/- 41.5% (p < 0.0001). CONCLUSIONS: An unexpected finding was that the pill count technique used in this study of elderly clients using chronic, repeat medications appeared to underestimate medication adherence. Numerous other limitations of pill count, self-report, and a province-wide prescription claims database in estimating medication adherence are presented. When using medication adherence as a process measure, the researcher and practitioner should be aware of the limitations unique to the data source they choose, and interpret data cautiously.

Aged↗
PubMedDate not supplied

Biotransformation of furosemide in patients with acute pulmonary edema.

Furosemide (20-80 mg) was administered iv over 5 min to 16 patients with the diagnosis of acute pulmonary edema due to left heart failure. Serum and urine samples collected during the 24 hr after administration were assayed for furosemide and its biotransformation products by gas-liquid chromatography. A biexponential decay of serum furosemide concentrations vs. time was observed. Recovery of furosemide and its metabolites from urine in 24 hr varied between 30 and 98% of the administered dose. The excretion of unchanged drug accounted for 22.6-73.4% of the dose. The excretion of the glucuronide metabolite and 2-amino-4-chloro-5-sulfamoylanthranilic acid accounted for 3.3-40.4% and from 0.13-3.92% of the dose, respectively. Urinary excretion of furosemide was less in patients with, than in those without, myocardial infarction. Urinary excretion of the oxidative acidic metabolite was increased in patients with reduced creatinine clearance. The glucuronide metabolite of furosemide was the major biotransformation product in these patients with acute pulmonary edema.

Acute Disease↗