摘要:

Background and objectiveClonidine in doses of 150 to 450 μg per day has been reported to reduce symptoms of craving associated with tobacco withdrawal and, in some cases, to improve long‐term abstinence rates of smoking cessation programs. However, subjects frequently experienced symptoms of dry mouth and drowsiness. This study investigated the lower end of the effective dose range of clonidine for smoking cessation to identify the lowest useful dose and thus minimize the adverse effects of the drug.MethodsA randomized, double‐blind, four‐way crossover design compared the effects of clonidine doses or placebo within individual subjects for 4 consecutive weeks. Smokers who were highly nicotine dependent were randomly assigned to different sequences of placebo and 300, 200, and 100 μg clonidine per day. Subjects were treated for 4 days of each treatment week and began smoking cessation from the end of day 2. Smokers recorded withdrawal symptoms on multiple visual analog scales during days 3 and 4 before resuming normal smoking until the next period of smoking cessation.ResultsA statistically significant dose‐response effect was found for craving scores (dose‐response gradient, −3.8/100 μg; 95% confidence interval [CI], −6.2 to −1.5;p= 0.002) but not for pooled tobacco withdrawal scores. The dose of 300 μg per day reduced mean craving scores significantly (− 16%; 95% CI, −31% to −1%). Dosing with 200 μg approached statistical significance (−14%; 95% CI − 30% to 1%) but dosing with 100 μg did not (−6%; 95% CI, − 22% to 9%). Troublesome adverse experiences were reported by more than 67% of subjects during 200 and 300 μg dosing.ConclusionsThis study showed a statistically significant dose‐response effect of clonidine on tobacco withdrawal craving and a reduction in mean craving scores of 16% during 300 μg dosing. However, its clinical usefulness is doubtful because of frequently reported adverse experiences.Clinical Pharmacology and Therapeutics

ISSN:0009-9236    

DOI:10.1038/clpt.1994.11

年代:1994

数据来源: WILEY

摘要:

ObjectiveTo examine the effect of frequency of oral administration of 1,2‐dimethyl‐3‐hydroxypyrid‐4‐one (LI) on urinary iron excretion.HypothesisSustained serum concentrations of LI will cause more iron chelation than the same daily dose given in larger but less frequent amounts.Patients and methodsTen patients with thalassemia with a mean age of 20.9 ± 4.7 years (range, 13 to 27 years), who were receiving regular treatment with 75 to 100 mg/kg/day oral LI, received 75 mg/kg/day LI orally in equally divided doses: every 6 hours for 3 days and every 12 hours for 3 days. The two study periods occurred 1 month apart immediately after the monthly blood transfusions. Urine was collected for two consecutive 24‐hour periods during each of the different schedules. Serial blood samples were collected from six patients over a 6‐hour period and analyzed for total LI and the LI glucuronide metabolite concentrations.ResultsThe patient's mean hemoglobin levels (138.8 ± 12.5 and 139.0 ± 11.6 gm/L) and ferritin levels (2856.4 ± 2207.8 and 2890.0 ± 2264.4 μg/L) were similar during the every‐6‐hour and every‐12‐hour LI administrations, respectively. There was significantly more urinary iron excretion when LI was administered every 6 hours (0.59 ± 0.29 mg/kg/day) versus every 12 hours (0.40 ± 0.26 mg/kg/day;p= 0.0129). Calculated 24‐hour area under the plasma concentration—time curve of LI was similar during the every‐6‐hour (7023.9 ± 2637.8 mg · min/L) and every‐12‐hour (7050.1 ± 1668.8 mg · min/L) experiments.ConclusionsThese data suggest that the sustained presence of LI in the blood results in greater chelation of iron than that observed with larger, less frequent doses.Clinical Pharmacology and Therap

ISSN:0009-9236    

DOI:10.1038/clpt.1994.12

年代:1994

数据来源: WILEY

摘要:

ObjectiveTo determine the frequency of congestive heart failure and cardiac conduction disturbances in elderly patients treated with topical glaucoma medications.MethodsThese case‐control studies were conducted among participants in the New Jersey Medicaid and Medicare program from 1986 to 1990. A total of 35,445 subjects (ages 65 to 99 years) were included in the congestive heart failure analysis, and 4278 subjects were included in the conduction disorder analysis.ResultsThe frequency of initiation of congestive heart failure therapy, defined as the new use of digoxin or furosemide, was not increased for users of topical glaucoma medications. The frequency of pacemaker placement was also not increased for topical glaucoma medication users. Analyses were adjusted for age, race, gender, nursing home or hospital status, number of prescription medications, and selected medication exposures. Advanced age and heavy use of other prescription medications were associated with an increased likelihood of both cardiovascular outcomes.ConclusionMajor cardiovascular side effects did not occur at an increased rate among patients using topical β‐blockers or other glaucoma medications compared with control subjects. This population‐based study places findings from case reports and small clinical trials in a broader context to help with clinical assessment of the risks and benefits of glaucoma therapy in the elderly.Clinical Pharmacology and Therapeutics(1994)55,76–83; doi:10.1038/clp

ISSN:0009-9236    

DOI:10.1038/clpt.1994.13

年代:1994

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1994)55,84–85; doi:10.1038/clpt.1994.

ISSN:0009-9236    

DOI:10.1038/clpt.1994.14

年代:1994

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1994)55,85–87; doi:10.1038/clpt.1994.

ISSN:0009-9236    

DOI:10.1038/clpt.1994.15

年代:1994

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1994)55,87–88; doi:10.1038/clpt.1994.

ISSN:0009-9236    

DOI:10.1038/clpt.1994.16

年代:1994

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1994)55,89–91; doi:10.1038/clpt.1994.

ISSN:0009-9236    

DOI:10.1038/clpt.1994.17

年代:1994

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1994)55,92–92; doi:10.1038/clpt.1994.

ISSN:0009-9236    

DOI:10.1038/clpt.1994.18

年代:1994

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1994)55,93–122; doi:10.1038/clpt.1994.

ISSN:0009-9236    

DOI:10.1038/clpt.1994.19

年代:1994

数据来源: WILEY