摘要:

Oral dipyridamole has been used in conjunction with thallium 201 imaging to diagnose coronary artery disease in patients unable to exercise. However, the pharmacokinetic disposition of high‐dose dipyridamole, particularly the time to maximum drug concentration, has not been described in patients undergoing oral dipyridamole‐thallium 201 scanning. Therefore, we measured serial concentrations in 20 outpatients undergoing thallium 201 testing after a single 400‐mg oral dose of dipyridamole. In patients with positive thallium scans (group A), concentrations were slightly higher than in those with negative scans (group B). The variability in concentrations for both groups ranged from 3–118%. The area under the dipyridamole concentration‐time curve from 0–4 hours ranged from 2.9–2.3 μg·hr/ml. The time to peak plasma level for dipyridamole ranged from 0.5–2.5 hours, with two patients having undetectable levels at the time of thallium 201 injection. Dipyridamole concentrations did not correlate with changes in diastolic or systolic blood pressure, or heart rate. Although it is unknown what concentration is required to produce changes in coronary flow velocity, use of oral dipyridamole in this setting resulted in highly variable concentrations. In addition, these data suggest that a small percentage of patients will not have detectable concentrations at the time of the first thallium 201 scan, possibly limiting the usefulness of this agent in conjunction with thallium scintigraphy

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03613.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

To compare the effect of age on pharmacokinetics of orally administered ofloxacin, two separate studies were reanalyzed using mixed‐effect modeling with the program NONMEM. Subjects were male volunteers, 36 age 65 years or greater and 24 age 18–40 years. The younger group received three 100‐mg tablets and the older group received two 200‐mg tablets of ofloxacin. Serial blood samples obtained throughout dosing were assayed for drug concentrations using high‐performance liquid chromatography. A pharmacostatistical model was developed for the data using mixed‐effect modeling with NONMEM. A one‐compartment open model with first‐order absorption, which included the covariables weight and age, best fit the data. Mean (SE) population values were clearance/F 0.219 (0.009) L/hr/kg, volume of distribution/F 1.50 (0.071) L/kg, and absorption rate constant 2.26 (0.048) hr−1. Older subjects had a 29% lower clearance and 13% lower volume of distribution then the

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03614.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

We compared the endoscopic effects and pharmacokinetic profiles of an experimental buccal formulation of piroxicam to oral capsules in an attempt to determine whether nonsteroidal antiinflammatory drug‐induced gastropathy is due to a local or systemic effect. Ten healthy subjects received 20 mg piroxicam daily in a double‐blind, randomized, crossover, placebo‐controlled study. Upper endoscopies were performed at the baseline and at the end of each 2‐week dosing arm of the study. Pharmacokinetic data obtained included serum and gastric piroxicam concentrations and serum 5′‐hydroxypiroxicam metabolite concentrations after the first dose and 2 weeks of dosing. No differences in endoscopy scores or patient symptom scores were noted between the two dosage forms after 2 weeks of dosing. Pharmacokinetic data of piroxicam and the metabolite revealed that the buccal formulation may not have been absorbed exclusively from the bu

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03615.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Troleandomycin (TAO) is an alternative agent used in the treatment of severe, steroid‐requiring asthma. Its mechanism of action, once thought to be inhibition of theophylline clearance, remains unclear. Twenty‐four‐hour theophylline profiles were obtained in 11 children with severe asthma prior to and after 2 and 12 weeks of low‐dose TAO therapy. Theophylline dosages were adjusted by blinded investigators to maintain serum theophylline concentrations (STCs) between 10 and 20 μg/ml. Dosages were decreased from 877 ± 60 mg/day (mean ± SEM) before TAO to 811 ± 56 mg/day (NS) after 2 weeks and 764 ± 56 mg/day (p<0.05) after 12 weeks. Because of the dosage adjustments, STCs did not increase significantly. Theophylline clearance was reduced from 65.7 ± 9.8 ml/kg/hour at baseline to 50.2 ± 4.1 ml/kg/hour (p<0.05) after 2 weeks and 50.1 ± 6.2 ml/kg/hour (p<0.05) after 12 weeks of TAO therapy. We conclude that TAO can significantly reduce theophylline clearance, resulting in increased STCs if dosages are not titrated. We recommend an empiric 25% reduction of daily theophylline dose with the initiation of TAO. We also recommend monitoring STCs 4 hours after the morning dose (with twice‐daily dosing of sustained‐release products) after 3, 7, 14, and 30 days of TAO therapy, then period

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03616.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The influence of fluoxetine on triazolam pharmacokinetics was studied because of changes in diazepam pharmacokinetics reportedly produced by fluoxetine. Twenty‐four healthy volunteers received a single 0.25‐mg triazolam tablet alone, and another 0.25‐mg tablet after 8 days of fluoxetine therapy 60 mg/day. All subjects received these treatments in the same sequence. Several blood samples were drawn from the subjects after the triazolam doses and were assayed by high‐performance liquid chromatography (HPLC). Blood samples were drawn immediately before the last three fluoxetine doses to determine the concentration of fluoxetine and its metabolite norfluoxetine, also by HPLC. The pharmacokinetics of triazolam did not change significantly when the tablets were administered after multiple doses of fluoxetine. These results indicate that no pharmacokinetic interaction exists between triazolam and fluoxetine or norfluoxetine. However, each patient's clinical response to therapy should be monitored when triazolam tablets and fluoxetine capsules are administered concom

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03617.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The bioavailability of controlled‐release morphine 30‐mg tablets (MSC) administered orally or rectally and immediate‐release morphine (RMS) 30‐mg suppositories per rectum, was compared in this 14‐subject, randomized, single‐dose, analytically blinded, crossover study. Rectal MSC plasma morphine area under the curve from 0–24 hours (AUC0–24) was 50.8% of RMS and was similar for MSC administered by either route (rectal MSC = 90% oral MSC). Rectal MSC had a significantly delayed time to peak plasma level (5.4 vs 1.07 and 2.5 hrs for rectal MSC vs RMS and oral MSC, respectively) and a significantly attenuated time to maximum concentration (6.1 vs 25.4 and 9.7 ng/ml, respectively). Proctoscopy 24 hours after insertion revealed seven instances of mild, transient mucosal erythema or edema with rectal MSC and 12 with RMS. The number of nonlocal adverse effects was 14 with rectal MSC, 19 with RMS, and 18 with oral MSC. Further studies must determine the therapeutic consequences of pharmacokinetic differences and establish guidelines for rectal MSC use. The product is currently not recommended by the manufacturer for rectal

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03618.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

We conducted a study to characterize a population of cocaine users who were referred to a state psychiatric institution, identify treatment problems including reasons for relapse, and develop strategies to improve treatment outcome. Using a data base system from a tertiary‐care hospital emergency department, we identified a sample of 80 patients with a cocaine‐related presentation who came to the emergency department and were referred to the psychiatric facility. Forty‐six percent had consumed crack cocaine, and 65% reported ingesting cocaine with other drugs, half of them with alcohol. Suicidal ideation or attempt was the most common reason for referral. A retrospective review of 58 of the 80 referrals to the psychiatric facility showed that over half of the patients were given a concurrent psychiatric diagnosis and required hospitalization on an acute‐care psychiatric unit. Sixty‐two percent of those admitted had prior hospitalizations at the psychiatric facility, yet only five patients had received treatment for substance abuse. Seventy‐four percent were readmitted to the psychiatric facility within 1 year of their index episode, with a higher rate of relapse among persons with dual diagnoses compared to cocaine users without dual diagnoses (p<0.05). Possible reasons for relapse included lack of referral for substance abuse treatment, nonintegrated treatment of psychiatric illness and substance abuse, lack of psychosocial support, and unresolved financial or job‐related stressors. The data support increased funding to facilities that treat persons with dual diagnoses, and suggest the need to develop comprehensive treatment approaches involving a multidisciplinary team to address issues of mental illness and substance abuse concomitantly, and to identify and resolve stressors leadi

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03619.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Ondansetron hydrochloride dihydrate is a 5‐hydroxytryptamine (5‐HT3) antagonist that was recently approved by the Food and Drug Administration for the treatment of chemotherapy‐induced emesis. The mechanism of action is thought to be due to competitive inhibition of specific serotonin receptors in the central nervous system and gastrointestinal tract. In clinical trials with cisplatin‐induced emesis, ondansetron resulted in complete control of vomiting (0–2 episodes) in 55–87% of patients during the first 24 hours of chemotherapy administration. It was significantly more effective than metoclopramide in comparative trials. Ondansetron is also being investigated for the treatment of radiation‐ and anesthesia‐associated nausea and vomiting. Studies in animals demonstrate potential efficacy in the treatment of anxiety, drug withdrawal, and schizophrenia. The drug is generally well tolerated, with no reported extrapyra

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03620.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The patient‐activated analgesic system was introduced in 1968. Early trials, although uncontrolled, supported the safety and efficacy of patient‐controlled analgesia (PCA) in several kinds of pain, such as that relating to surgery, cancer, trauma, and obstetric procedures. In the past decade, prospective, randomized trials have reported several advantages of PCA over conventional analgesia in the early postoperative period. Although not supported by all controlled trials, they include improved pain relief, less sedation, lower level of narcotic consumption, fewer postoperative complications, greater patient satisfaction, and improved pulmonary function. Preliminary results in the management of chronic pain indicate that PCA can lead to significant lifestyle improvements in ambulatory patients with cancer. The most significant, although infrequent, adverse effect is respiratory depression, the majority of cases occurring in patients predisposed secondary to concomitant illness or as a result of human error. The clinical use of PCA will likely see a significant increase among persons with cancer, and an increase in epidural administration. The cost benefit of PCA has yet to be assessed in inpatient and outpatient setti

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03621.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb03622.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY