ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05606.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abusable psychotropic use can, and does, affect all North American youth, either directly or indirectly, regardless of age, gender, culture, ethnic background, education, race, or socioeconomic status. Over the last decade, the morbidity and mortality associated with abusable psychotropic use among youth have become staggering. A current overview of the phenomenon of abusable psychotropic use among youth in North America, including the use of alcohol, cannabis, cocaine, LSD, nicotine, and polyabusable psychotropic use, is presented with attention to the expanding role of clinical pharmacologists in relation to both prevention and treatment. The Mega Interactive Model of Abusable Psychotropic Use Among Youth is presented as a heuristic device to assist clinical pharmacologists, and other health care providers, in addressing the multifactorial interactive aspects of this complex phenomenon as observed in the pediatric age group. In this regard, attention is given to the interaction of the Abusable Psychotropic Dimension, including the Abusable Psychotropic Variables (e.g., pharmacokinetics, abuse potential) and Pattern of Use Variables (e.g., social use, abuse, compulsive use), with the Young Person, Societal, and Time Dimensions.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05607.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The role of serotonin as the possible trigger mechanism of vomiting associated with chemotherapeutic drugs was further investigated in cancer patients (n=86). Increases in 5‐hydroxyindoleacetic acid (5‐HIAA) excretion rates (2.5–2.9 times baseline values) were observed 4 to 8 hours after high‐dose cisplatinum (≥50 mg/m2). The daily excretion of 5‐HIAA from 24–48, 48–72, and 72–96 hours after cisplatinum was not different from pre‐cisplatinum levels. These results, together with the efficacy data for 5‐HT3 antagonists, suggests that serotonin may trigger the early, intense period of emesis, but not the period of delayed emesis, following high‐dose cisplatinum. Compared with the first cycle of chemotherapy, higher peak levels and more sustained elevations of 5‐HIAA excretion were found after subsequent cycles, with high‐dose cisplatinum. Further, no evidence of serotonin depletion was found after a single or after repeated cycles of treatment with high‐dose cisplatinum. These data suggest that the more intense emetic response associated to repeated cycles of treatment may be triggered by greater changes in serotonin release. No significant differences in the rate and amount of 5‐HIAA excreted induced by low‐dose (30±2 mg/m2) and high‐dose (84±3 mg/m2) cisplatinum were found between those patients who received dexamethasone (D) (20 mg IV) and those who received metoclopramide (M) (2 mg/kg, IV), irrespectively of the cycle of treatment. Interestingly, for M but not for D, best antiemetic protection was observed when lower amounts of serotonin were released (i.e., low‐dose cisplatinum and initial cycles of treatment). This suggests, that contrary to D, the effects of M, a purported antagonist of 5‐HT3 receptors, are highly dependent on the quantity of serotonin release induced by a chemotherapeutic drug. Finally, our data suggest that D does not interfere w

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05608.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Twelve cancer patients (aged 49–74 years) receiving doxorubicin (66 ± 8 mg/m2) as a 1‐hour intravenous infusion had serial serum samples (0–48 hours) obtained after the first and second courses of therapy. Mean number of days between courses was 24.3, and all patients had normal liver function. Patients received the same concomitant antineoplastic agents and doses in both courses. Doxorubicin and doxorubicinol concentrations were assayed by high‐performance liquid chromatography and fitted to a two‐ or three‐compartment infusion model. White blood cell and platelet toxicity were evaluated as (initial — nadir/initial)* 100. Differences in pharmacokinetic parameters were determined by a paired t test. Wide intrapatient and interpatient variability was seen between therapeutic courses. A significant decrease in the apparent volume of distribution of the central compartment (Vc= 16.6 versus 10.4 L/m2; P<.05), and a nonsignificant decrease in clearance (CL = 748 versus 658 mL/min/m2) was observed on the second course of therapy. Doxorubicinol area under the curve and elimination half‐life were similar between courses. Extensive chemotherapy‐induced changes in white blood cell and platelet counts were observed but were similar in degree for courses 1 and 2. These data suggest that higher initial doxorubicin concentrations on the second course of therapy are secondary to an alteration in distribution volume (Vc). In this subset of patients, however, these changes were not associated with an increase in he

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05609.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This study examined the disposition of olsalazine and its metabolites into breast milk after the ingestion of a single dose of 500 mg olsalazine. Blood and serum samples were obtained for 48 hours after the ingestion of 500 mg olsalazine in a 39‐year‐old lactating woman. Blood samples were obtained at .0, .5, 1, 2, 4, 6, 24.5, 26, and 48 hours. Maternal milk samples were obtained at .0, .5, 2, 4, 6, 14, 24, 28, 36, and 48 hours. Olsalazine and olsalazine‐S underwent high‐pressure liquid chromatography analysis, and 5‐ASA and Ac 5‐ASA underwent fluorometric detection. Acetylated‐5‐ASA achieved concentrations of .8, .86, and 1.24 μmol/L in breast milk at 10,14, and 24 hours, respectively. Olsalazine, olsalazine‐S, and 5‐ASA were undetectable in the breast milk for 48 hours after drug administration. Clinically significant drug exposure in the breast‐fed infant is unlikely after a maternal single dose of olsalazine. Idiosyncratic hypersensitivity, however, remains a possibility even if the infant is exposed to

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05610.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

A reflectance spectrophotometric method for evaluation of the skin blanching response to topical corticosteroids was evaluated. This blanching response is used, for drug development and regulatory purposes, to assess potency and bioequivalence of topical corticosteroid products. The common method involves the use of a human rater to measure blanching response in the skin. This study evaluated an instrumental alternative to the human rater and used this method to measure the differences between a number of brand name and generic topical corticosteroid products (six creams and six ointments). Products were applied to the forearms of normal volunteers and the blanching responses were assessed after 6 and 16 hours in both occluded and non‐occluded skin sites. Only the fluocinolone acetonide generic and brand name preparations were different from each other. The spectrophotometric method proved to be equivalent but not superior to the standard human observer metho

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05611.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Release of 5‐ASA from a sustained release formulation (Pentasa®, Ferring A/S, Copenhagen, Denmark) was monitored with plasma sampling for up to 24 hours in nine volunteers under both fasted and fed conditions. Drug absorption was correlated with location of the sustained‐release microgranules in the gastrointestinal tract by gamma scintigraphy. Disintegration of the labeled tablet preparation occurred in the stomach within 20 minutes and acetylated 5‐ASA was detectable in the plasma less than 60 minutes after ingestion. No significant differences were detected in either transit times through the small intestine, peak plasma acetylated 5‐ASA concentration or lag time to absorption between fasted and fed individuals. Peak plasma concentration of acetylated 5‐ASA usually occurred when the microgranules were present in the small intestine or ascending colon. The pharmacoscintigraphic study confirmed that 5‐ASA release from the formulation occurred throughout the gastrointestinal tract, and that food effects on the in vivo behavior of the preparation

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05612.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The pharmacokinetics of clarithromycin and its active 14(R)‐hydroxy metabolite were evaluated after single and multiple oral doses of 250 and 500 mg of clarithromycin. Multiple‐dose regimens used 12‐hour dosing intervals for 7 doses. Plasma and urine concentrations were measured using high‐performance liquid chromatography. Appearance of clarithromycin and its metabolite in plasma were rapid, as reflected by mean times to maximum plasma concentration ranging from 1.8 to 2.6 and 1.8 to 2.9 hours, respectively. The rises in clarithromycin peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) were disproportionate to increase in dose, suggesting nonlinearity in parent compound pharmacokinetics. Clarithromycin terminal disposition half‐life (t1/2) also exhibited dose dependency, ranging from harmonic means of 2.7 to 4.8 hours. In contrast, based on Cmax AUC, and predicted/observed accumulation ratios, nonlinearity in metabolite pharmacokinetics was not observed. Plasma accumulation of metabolite occurred to a much lesser degree than that of the parent compound despite a substantially longer t1/2 for the metabolite (metabolite accumulation ratios based on AUC dose 7/AUC dose 1:250‐mg regimen = 1.03 ± 0.33,500‐mg regimen = 0.81 ± 0.29, parent accumulation ratios: 250‐mg regimen = 1.64 ± 0.47, 500‐mg regimen = 1.65 ± 0.69). This would suggest that formation of this metabolite is capacity‐limited and that this may in part account for the nonlinearity observed in clarithromycin pharmacokinetics. Urinary excretion constituted a relatively important route of elimination of clarithromycin, with renal clearance accounting for 17 to 31% of appare

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05613.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Quinidine and nifedipine appear to be subject to metabolism by the same isozyme of cytochrome P‐450. In addition, both drugs have been reported to alter the pharmacokinetics of other compounds. To investigate a potential interaction, 10 healthy subjects (five male, five female) received quinidine sulfate (200 mg orally), nifedipine (20 mg orally), or the combination of both drugs every 8 hours for 4 doses using a randomized, cross‐over study design with a 2‐week washout period between treatments. Drug concentration, heart rate, and mean arterial pressure were measured at frequent intervals after the final dose. Quinidine concentrations were unchanged by the co‐administration of nifedipine. Nifedipine area under the curve (AUC0–8) increased 36.6% from 333 to 455 μg · hr/L (P<.05) after quinidine administration. Heart rate was significantly higher in the nifedipine‐quinidine treatment at 0.5, 1.0, 1.5, and 2.0 hours when compared with either drug alone. The maximum increase in heart rate (17.9 beats/minute) occurred at 0.5 hours after nifedipine administration and was significantly correlated with serum concentrations at that time (r = .78). These results suggest that quinidine inhibits nifedipine metabolism, and this pharmacokinetic interaction results in enhanced pharmacol

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05614.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

To evaluate the natriuretic effect of a nonhypotensive dose of felodipine, 11 healthy volunteers (age: 21–28 years) on a high‐sodium diet received the drug or its vehicle in a double‐blind, randomized, crossover study. Administered intravenously at a dose level of 7.5 μg/min for 30 minutes followed by 5 μg/min for 120 minutes, felodipine increased natriuresis (546 ± 69 vs. 454 ± 39 μmol/min, P<0.001) and diuresis (8.9 ± 0.6 vs. 7.5 ± 0.5 mL/min), compared to its vehicle. Renal plasma flow tended to be augmented, but there was a significant reduction of renal vascular resistance (0.085 ± 0.004 vs. 0.101 ± 0.012 mm Hg/mL/min, P<0.03). The glomerular filtration rate was slightly decreased and proximal sodium reabsorption was diminished with no measurable effect on distal function. Felodipine stimulated plasma renin activity, but produced no changes in plasma atrial natriuretic factor, cGMP, aldosterone, and atrial vasopressin levels. In conclusion, felodipine induced natriuresis and diuresis while reducing proximal tubular sodiu

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb05615.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY