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Biomedical subjects

L Fleckenstein

Publications and source records attributed to L Fleckenstein.

33 records · Page 2Linked to original sources
PubMed1988

Pharmacokinetics of antimony during treatment of visceral leishmaniasis with sodium stibogluconate or meglumine antimoniate.

5 patients with visceral leishmaniasis were treated with sodium stibogluconate (2 patients) or meglumine antimoniate (3 patients) given intramuscularly at a dose of 10 mg antimony (Sb) per kg body weight daily for 30 d. Blood samples were obtained at intervals during treatment and blood Sb concentrations measured by anodic stripping voltametry. The pharmacokinetics of both drugs were remarkably similar, with peak concentrations of approximately 10 mg/litre occurring 2 h after the initial dose. Most of the Sb was eliminated rapidly, but nadir Sb concentrations increased gradually during treatment from 0.04-0.08 mg/litre 24 h after the first dose to 0.19-0.33 mg/litre 24 h after the 30th dose. For both drugs, the data were best described by a two compartment, three term pharmacokinetic model representing an initial absorption phase with a mean half-life of 0.85 h, a rapid elimination phase with a mean half-life of 2.02 h, and a slow elimination phase with a mean half-life of 76 h. The slow terminal elimination phase may be related to in vivo conversion of pentavalent Sb to trivalent Sb, which could contribute to the toxicity associated with long-term high dose therapy.

Antimony↗
PubMed1983

Pharmacokinetics of chloroquine diphosphate in the dog.

Chloroquine diphosphate was administered i.v. and orally to seven male beagle dogs. Approximately 2 mg/kg was administered i.v. and 4 weeks later a single 150-mg (tablet) dose was administered orally. Blood sampling was carried out for 28 and 42 days, respectively, and whole blood drug levels were assayed by fluorometry. After i.v. injection, the chloroquine blood concentration-time profile exhibited a biexponential decay. The mean terminal T 1/2 was 12.6 days using i.v. data alone and 14.5 days with simultaneous fitting of oral and i.v. data. Pharmacokinetic parameters calculated using model-independent methods showed good agreement with model-dependent methods. The model-independent value for blood clearance was 2.67 liters/kg/day. A mean Vdss of 53.3 liters/kg indicates that the drug is widely distributed to tissues. Using a specific thin-layer chromatographic method, chloroquine and its major metabolite, desethylchloroquine, could be detected in blood for 42 days after oral chloroquine administration. These data suggest a long T 1/2 for the metabolite, as well as the parent drug. Chloroquine, desethylchloroquine and bisdesethylchloroquine were tested for in vitro activity against clinically derived chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Against chloroquine-sensitive P. falciparum, desethylchloroquine was as active as chloroquine, whereas bisdesethylchloroquine was less active. Against a chloroquine-resistant strain, desethylchloroquine was less active than chloroquine and bisdesethylchloroquine possessed no detectable activity.

Absorption↗
PubMed1982

Comparison of the disposition of total and unbound sulfisoxazole after single and multiple dosing.

Plasma concentrations of total and unbound sulfisoxazole were followed after single intravenous and oral doses of 1 g sulfisoxazole and during a 500-mg, four-time-a-day dosing regimen in six healthy males, using a specific high pressure liquid chromatographic assay method. Saturable plasma protein binding was observed at total concentrations above 80-100 mg/liter. The clearance of sulfisoxazole was 18.7 +/- 3.9 ml/min for total drug and 232 +/- 64 ml/min for unbound drug. Renal elimination, on the average, accounted for 49% of the clearance of sulfisoxazole. The apparent volume of distribution for total drug was 10.9 +/- 2.0 liters and 136 +/- 36 liters for unbound drug, indicating that sulfisoxazole is primarily distributed extracellularly. Accumulation of N4-acetyl-sulfisoxazole during multiple dosing did not affect the disposition of sulfisoxazole. Adjusting for variable renal clearances between oral and intravenous administration and using the unbound plasma concentrations, the bioavailability for an oral dose of sulfisoxazole was found to be 0.95 +/- 0.04.

Administration, Oral↗
PubMed1982

Comparative bio-availability characteristics of different brands of chloroquine available in Nigeria.

The disintegration, dissolution and bio-availability characteristics of six of the most popular brands of chloroquine used in Nigeria were determined in order to test the hypothesis that there are no significant differences among the different brands. The disintegration times of all the six brands ranged from 8.9 to 40.4 min while the dissolution times ranged from 17.5 to 60 min. All passed the U.S. Pharmacopoiea (USP) XX disintegration test. Bio-availability studies done on two brands, Avloclor (ICI) with the fastest dissolution rate and Pfizerquine (Pfizer) with the slowest dissolution rate, showed similar areas under the curve (AUC). Furthermore, their peak height concentration (Cmax) and time of peak height concentration (Tmax) did not show any significant differences. Consequently, statements about any of these six brands of cloroquine having a greater efficacy than the other may be pure conjecture.

Animals↗
PubMed1976

Oral contraceptive patient information. A questionnaire study of attitudes, knowledge, and preferred information sources.

A questionnaire was designed to assess attitudes, knowledge, and views and sources of drug information on oral contraceptives, with particular attention to the role of the patient-oriented package insert. An analysis of 828 completed questionnaires shows that many women are apprehensive about the safety of oral contraceptives. The impact of the patient-oriented oral contraceptive insert on the women surveyed appears to be positive. The present labeling is read and found useful by most oral-contraceptive users. Patients were variably informed about the correct use and side effects discussed in current labeling, suggesting a need for improved transmission of important drug information. Patients preferred information from health professionals and printed sources over media sources. Balanced label information about risks of oral contraceptives should be made available to improve the likelihood of sound risk-benefit judgments.

Adolescent↗
PubMed1976

Sodium salicylamide: relative bioavailability and subjective effects.

The bioavailability of sodium salicylamide (NaSAM) in solution of salicylamide (SAM) tablets was compared in 6 healthy human volunteers. Bioavailability was assessed by plasma level determinations of nonmetabolized salicylamide (free SAM) and salicylamide plus conjugated metabolites (total SAM) for 3 hr following oral doses of 0.65, 1.30, 1.95, and 2.60 gm of salicylamide. The availability of NaSAM was found to be superior to SAM and dose-dependent. Mean peak levels of free SAM and total SAM were higher and were reached earlier after NaSAM liquid than after SAM tablets. Significantly higher mean levels of free SAM were found at the 1.95 and 2.60 gm dose levels after NaSAM administration than after SAM. Mean total SAM concentration was significantly higher after NaSAM at all dosage levels. The sedative effects of salicylamide were assessed with a self-scoring questionnaire. Sedation seemed to increase with increasing dose of both NaSAM and SAM. The sedative response occurred earlier after NaSAM than after SAM. Side effects were minor and transient in nature, occurred at the higher dosage levels, and were predominantly lightheadedness and dizziness. Because NaSAM produces higher drug levels and has a more rapid onset of subjective effects, we conclude that it represents a potentially superior dosage form.

Biological Availability↗
PubMed1976

Correlation between electrocardiographic changes, serum digoxin, and total body digoxin content.

Serial electrocardiograms and serum digoxin levels were obtained in four healthy volunteers receiving daily doses of digoxin, 0.25 mg for the first two weeks and 0.5 mg for two more weeks. We found a linear relationship between serum digoxin levels and the "PTQ index" (a function of the PR-interval, corrected QT-time, and T-wave depression). In 3 of the 4 subjects the correlation was statistically significant. The degree of linear correlation was improved when PTQ was correlated with the computer-calculated total body burden of digoxin.

Adult↗
PubMed1975

Savings from generic prescriptions. A study of 33 pharmacies in Rochester, New York.

Brand name and gereric prescriptions for 12 drugs were surveyed at 33 pharmacies in the Rochester, New York, area to determine how frequently generic prescriptions were filled with a product other than the major brand, and at a savings to the consumer. Generic prescriptions for ampicillin, erythromycin, propoxyphene, and dioctyl sodium sulfosuccinate were often filled at prices lower than comparable brand name prescriptions. Occasional, but often substantial, savings were obtained for papaverine, pentaerythritol tetranitrate, and conjugated estrogens. No savings were obtained for penicillin V, chlorpheniramine, diphenylhydantoin, sulfisoxazole, or methenamine mandelate. The pharmacists included in the survey identified correctly a mean of 18.5 out of 22 drugs as to whether products other than the major brand were available. A sample of physicians identified correctly a mean of 14.1 drugs. Pharmacists who were better informed as to which drugs were available generically were more likely to stock alternative products and more likely to charge lower prices on generic prescriptions than on brand name prescriptions.

Alkanesulfonates↗
PubMedDate not supplied

Primaquine disposition in the isolated perfused rat liver: effect of mefloquine induced bile flow reduction.

The disposition of primaquine (0.75 mg, 5 microCi) has been investigated in the isolated perfused rat liver (IPRL) preparation alone and concurrently with mefloquine. In both groups, primaquine concentrations declined exponentially. There were no significant differences between the respective groups in the half-lives (2.5 +/- 1.5, 2.2 +/- 1.1 h), AUCs (0.43 +/- 0.14, 0.372 +/- 0.096 microgram.h ml-1), clearances (19.0 +/- 5.4, 21.1 +/- 4.2 ml h-1), and apparent volume of distribution (78.9 +/- 28.1, 76.2 +/- 31.7 ml). In the presence of mefloquine, total bile production was significantly reduced (1244.5 +/- 317.1 microliters) compared with primaquine alone (1621.5 +/- 174.2 microliters). Hence, although significantly less radioactivity ([3H]) was eliminated in bile in the presence of mefloquine (30.0 +/- 7.9 per cent versus 39.9 +/- 3.6 per cent) there was no significant difference between the groups in [3H]/microliters bile eliminated. Significantly more [3H] was recovered from the livers of the mefloquine/primaquine group. This was underlined by the significantly greater proportions of [3H] recovered from the 10,000 g pellet, 10,000 g supernatant and 105,000 g supernatant in the presence of mefloquine compared with primaquine alone. Hence, it appears mefloquine had little or no direct action or primaquine metabolism, but significantly reduced bile production.

Animals↗
PubMedDate not supplied

Pharmacokinetics and disposition of WR-1065 in the rhesus monkey.

The pharmacokinetics of WR-1065 [S-2-(3-aminopropylamino)ethanethiol] were investigated following iv, intraduodenal, and intraportal administrations in the rhesus monkey. Pharmacokinetic parameters were estimated by compartmental modeling of plasma concentration data from 10-min and 120-min iv infusions. Higher apparent volumes of distribution (Vc and Vss) and higher mean residence time (MRT) were observed at the slower infusion rate but a constant total dose. The values reflect a change in the distribution of WR-1065, possibly due to to saturation of binding in plasma and tissue. However, clearance remained unchanged. For a monkey administered approximately twice the 60 mg/kg dose infused over 120 min, data analysis indicates a disproportional increase in AUC and a substantial decrease in clearance. Low and erratic plasma concentrations of free drug (analytically determined without reductive cleavage) were observed following intraduodenal administration of WR-1065, demonstrating the drug's poor oral bioavailability. Results of intraduodenal administrations of radiolabeled drug indicated than an appreciable amount of the radiolabel in the dose reached the systemic circulation. However, after either intraduodenal or iv administration, only 31% of the AUC (radiolabel) could be accounted for as total (free and disulfide-bound) WR-1065 by specific analysis in separate experiments. Low levels of total cysteamine strongly suggest it to be a minor contributor to the disposition of the drug. Free WR-1065 AUC values following intraportal administration were similar to values obtained after iv administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Disposition of the radioprotector ethiofos in the rhesus monkey. Influence of route of administration.

Plasma concentrations of ethiofos [S-2-(3-aminopropylamino)ethyl phosphorothioic acid, WR-2721] were compared following iv, ip, intraduodenal, and portal administration to the rhesus monkey. Plasma samples were analyzed for ethiofos, free WR-1065, [2-(3-aminopropylamino)ethanethiol], and total material convertible to WR-1065 (total WR-1065). In separate experiments, total radioactivity in plasma was compared following iv, ip, and intraduodenal administration of [14C]ethiofos; excretion of the radiolabel was measured in urine and in feces. Intraduodenal administration of unlabeled ethiofos rarely gave measurable levels of unchanged drug in plasma. In contrast, intraduodenal administration of [14C]ethiofos produced an average AUC for total radioactivity that was 62% of that for a 10-min iv infusion of [14C]ethiofos. Urinary excretion of radioactivity following iv and intraduodenal administration of [14C]ethiofos was 78.9 +/- 14.0% and 43.8 +/- 12.4%, respectively, whereas 1.9 +/- 0.5% and 9.7 +/- 6.3% was excreted in feces. After an ip dose of either labeled or unlabeled ethiofos, absorption of the dose was prolonged, but AUC values for total radioactivity or ethiofos and total WR-1065 were similar to those observed after the corresponding 10-min iv experiments. For either iv or portal routes, increases in ethiofos AUC values were observed for the same total dose when the infusion rate was increased from 1.25 to 15 mg/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Amifostine↗