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Investigation of in vitro transdermal absorption of fentanyl from patches placed on skin samples obtained from various anatomic regions of dogs.

OBJECTIVE: To investigate in vitro transdermal absorption of fentanyl from patches through skin samples obtained from various anatomic regions of dogs. SAMPLE POPULATION: Skin samples from 5 Greyhounds. PROCEDURE: Skin samples from the dogs' thoracic, neck, and groin regions were collected postmortem and frozen. After samples were thawed, circular sections were cut and placed in Franz-type diffusion cells in a water bath (32 degrees C). A commercial fentanyl patch, attached to an acetate strip with a circular hole, was applied to each skin sample. Cellulose strips were used as control membranes. Samples of receptor fluid in the diffusion cells were collected at intervals for 48 hours, and fentanyl concentrations were analyzed by use of high-performance liquid chromatography. RESULTS: Mean+/-SD release rate of fentanyl from the patch, defined by its absorption rate through the non-rate-limiting cellulose membrane, was linear during the first 8 hours (2.01+/-0.05 microg/cm2 of cellulose membrane/h) and then decreased. Fentanyl passed through skin from the groin region at a faster rate and with a significantly shorter lag time, compared with findings in neck or thoracic skin samples. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro, fentanyl from a patch was absorbed more quickly and to a greater extent through skin collected from the groin region of dogs, compared with skin samples from the thoracic and neck regions. Placement of fentanyl patches in the groin region of dogs may decrease the lag time to achieve analgesia perioperatively; however, in vivo studies are necessary to confirm these findings.

Administration, Cutaneous↗

Abstinence from smoking reduces incisional wound infection: a randomized controlled trial.

OBJECTIVE: Clinical studies show that the incidence of postoperative wound complications is higher in smokers than nonsmokers. In this study, we evaluated the effect of abstinence from smoking on incisional wound infection. METHODS: Seventy-eight healthy subjects (48 smokers and 30 never-smokers) were included in the study and followed for 15 weeks. In the first week of the study, the smokers smoked 20 cigarettes per day. Subsequently, they were randomized to continuous smoking, abstinence with transdermal nicotine patch (25 mg per day), or abstinence with placebo patch. At the end of the first week and 4, 8, and 12 weeks after randomization, incisional wounds were made lateral to the sacrum to excise punch biopsy wounds. At the same time identical wounds were made in 6 never-smokers. In 24 never-smokers a wound was made once. All wounds were followed for 2 weeks for development of wound complications. RESULTS: A total of 228 wounds were evaluated. In smokers the wound infection rate was 12% (11 of 93 wounds) compared with 2% (1 of 48 wounds) in never-smokers (P <0.05). Wound infections were significantly fewer in abstinent smokers compared with continuous smokers after 4, 8, and 12 weeks after randomization. No difference between transdermal nicotine patch and placebo was found. CONCLUSIONS: Smokers have a higher wound infection rate than never-smokers and 4 weeks of abstinence from smoking reduces the incidence of wound infections.

Adult↗

Drug- and temperature-induced changes in peripheral circulation measured by laser-Doppler flowmetry and digital-pulse plethysmography.

We measured the effects of a new transdermal nitroglycerin patch (25 mg, 10 cm2) applied for 24 h, norphenephrine (6 mg), prazosin (1 mg) as well as local heat and cold provocation on blood pressure, heart rate, skin blood flow (measured by laser-Doppler flowmetry, L-D) and peripheral arterial resistance (assessed by digital pulse plethysmography, D-P) in 15 healthy volunteers (aged 21-31 years). Heat provocation induced a three-fold increase in skin blood flow in the hand (p less than 0.001) and cold provocation a decrease in flow (p less than 0.05) of about 20%. Forehead skin blood flow did not change. Peripheral arterial resistance showed less consistent changes during the provocation tests. Prazosin increased the forehead skin blood flow (p less than 0.01) and decreased peripheral arterial resistance, while norphenephrine showed an opposite effect. Transdermal nitroglycerin induced an increase of 25% in forehead skin blood flow (p less than 0.05) which persisted for 24 h and a decrease in peripheral arterial resistance (p less than 0.02), but this effect was evident up to 8 h only. We conclude that (1) local heat and cold provocation mainly affected skin blood flow, (2) vasodilative and vasoconstrictive drugs showed marked changes in peripheral arterial resistance, but at different points in time from subject to subject, and (3) transdermal nitroglycerin patches induced haemodynamic changes persisting for up to 8-24 h.

2-Hydroxyphenethylamine↗

Effect of smoking and abstention on oxidative burst and reactivity of neutrophils and monocytes.

BACKGROUND: Smoking is associated with surgical wound infections, impaired wound healing, and tissue-destructive disorders. The mechanisms are largely unknown, but changes in the function and activity of inflammatory cells may be involved. METHODS: Seventy healthy volunteers (54 smokers and 16 never smokers) were included. The smokers were studied while they smoked and after 20 days of abstinence. After the first 10 days of abstinence, they were randomized to double-blind treatment with transdermal nicotine patch 25 mg per day or placebo. Venous blood neutrophils and monocytes were sampled and isolated. In 22 randomly selected smokers and in all never smokers, the oxidative burst and chemotaxis were determined by a chemiluminescence response assay and a modified Boyden chamber technique, respectively. Stimulants were opsonized zymosan, formyl-Met-Leu-Phe, and zymosan-activated serum. RESULTS: The neutrophil and monocyte oxidative burst was 50% and 68% lower, respectively, in smokers compared to never smokers (P < .05). Neutrophil chemotaxis was 93% higher in smokers (P < .05). Monocyte chemotaxis was lower in smokers compared to never smokers (P < .05). After 20 days of abstinence, neutrophil oxidative burst increased to the level of never smokers (P < .05); monocyte oxidative burst increased by 50% (P < .05). Chemotaxis was only marginally affected. The changes induced by abstinence were less pronounced in the transdermal nicotine patch group compared to the placebo group. CONCLUSIONS: Smoking attenuates the oxidative burst of inflammatory cells and increases chemotaxis. Three weeks of abstinence normalize the oxidative burst, but affect chemotaxis only marginally.

Administration, Cutaneous↗

Transdermal administration of clonidine: a new approach to antihypertensive therapy.

This study assessed the antihypertensive efficacy and side effects of clonidine administered transdermally. Twenty-five patients with mild to moderate essential hypertension (seated diastolic blood pressure 95-120 mm Hg with diuretic therapy alone) controlled with oral diuretic plus oral clonidine were enrolled. Transdermal clonidine was substituted for oral clonidine and titrated until adequate blood pressure control (seated diastolic blood pressure less than 90 mm Hg) was attained. At the end of titration, seated morning blood pressure averaged 129/90 +/- 15/5 mm Hg (mean +/- standard deviation) compared to 136/96 +/- 13/7 mm Hg (p less than 0.01/0.001) during oral clonidine administration. Standing morning blood pressure was also lower during transdermal than oral therapy (131/94 +/- 16/5 vs 136/99 +/- 14/7, p less than 0.05/0.001). Afternoon blood pressures (at peak effect of oral dose) were virtually identical during oral and transdermal therapy in both seated and standing positions. Typical side effects of oral clonidine, including dry mouth, drowsiness, and sexual dysfunction, were reduced during transdermal therapy. There was less morning-to-afternoon variability of blood pressure control and plasma clonidine concentrations during transdermal than during oral therapy. One patient left the study because of drowsiness and two because of skin reactions to the transdermal skin patch. Mild transient local skin irritation occurred frequently. Transdermal clonidine plus a diuretic is an effective treatment for mild to moderate essential hypertension, improves compliance and reduces side effects of therapy.

Administration, Topical↗

Smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy.

Effects of smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy were investigated in two studies. A total of 403 smokers underwent nine weeks of behavioral self-control treatment. For seven weeks, groups with transdermal nicotine substitution were also provided with nicotine patches that continuously release nicotine through the skin into the circulatory system. The effects of treatment were measured by total abstinence. The results showed that the nicotine concentration in the patch, special relapse prevention methods, and the type of dosage (individual versus fixed dose) had no influence on therapeutic success. Nicotine concentration played a decisive role in the compatibility of the patch. Combining transdermal nicotine substitution with behavioral therapy produced 12-month success rates (total abstinence) of about 35%.

Administration, Cutaneous↗

Are there sex differences in transdermal nicotine replacement therapy patch efficacy? A meta-analysis.

Smoking-related death and disability rates for women have risen sharply recently. Despite lower smoking cessation success rates for women using behavioral therapies, data are limited on whether specific pharmacological therapies are equally efficacious in men and women. Using meta-analytic techniques, we examined whether significant differences in therapeutic efficacy of nicotine replacement therapy (NRT) for smoking cessation exist by sex. Out of the 31 randomized clinical trials of NRT that met inclusion criteria, 11 contributed to the analysis. The odds ratios for NRT vs. placebo were derived from each trial separately by sex for males and females, and these ratios were combined to give a pooled estimate of the effect of sex in response to NRT. NRT was effective at all time points in men (< 6 months: OR = 2.05, 95% CI= 1.61-2.60; 6 months: OR = 1.98, 95% CI = 1.51-2.60; 12 months: OR = 1.86, 95% CI = 1.39-2.50) and women (< 6 months: OR = 2.09, 95% CI = 1.65-2.65; 6 months, OR = 1.52, 95% CI = 1.17-1.98; 12 months: OR = 1.63, 95% CI = 1.22-2.18). At all time points, no significant difference was observed between sexes (< 6 months: OR = .97, 95% CI = .69-1.36; 6 months: OR = 1.33, 95% CI = .91-1.95; 12 months: OR = 1.21, 95% CI = .79-1.84). The results of this meta-analysis do not support the hypothesis that NRT has higher therapeutic efficacy for men than women.

Administration, Cutaneous↗