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Estradiol and estrone plasma levels during application of three strengths of a 7-day estradiol transdermal patch.

BACKGROUND: A new estradiol transdermal patch was developed for a once weekly application, with the aim to achieve an optimum practicability and to improve long-term compliance with estrogen replacement therapy. The pharmacokinetics of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during a 7-day application of the new patch is reported in this publication. METHODS: Unconjugated estradiol and estrone were assayed in plasma in a three-way crossover study on 18 postmenopausal women during and after a 7-day application of 3 strengths of the new patch, with daily release rates of 25, 50 and 75 micrograms of estradiol. RESULTS: During the 7-day application of the transdermal patches the concentration in plasma of unconjugated estradiol increased from less than 5 pg/ml, typical of postmenopause, to average concentrations of 26, 49 and 66 pg/ml under the patches with the release rates of 25, 50 and 75 micrograms/day of estradiol, respectively. The increases were linearly related and proportional to the strength of the patches. Upon removal of the patches, the estradiol concentrations returned to the basal postmenopausal values in 8-24 h. Retarded with regard to estradiol, there was also an increase of unconjugated estrone, from basal concentrations of 24 pg/ml to average concentrations of 39, 54 and 62 pg/ml, respectively. Estrone returned to its basal concentrations 24-48 h after removal of the patches. The estradiol/estrone ratio from the low pre-treatment values of 0.15-0.21 typical of postmenopause increased to average values of 0.51, 0.92 and respectively 1.09 during the application of the patches with the three strengths. The ratios are in the range of those of unconjugated hormones during the fertile age of women. The patches were well tolerated by the skin, with rare mild and transient reactions that disappeared spontaneously and did not cause interruption of treatment. Also the systemic tolerability was good, with occasional mild or moderate side effects typical of estradiol found especially under the application of the two higher strengths, i.e. with release of 50 and 75 micrograms/day of estradiol. CONCLUSIONS: The effective pharmacokinetic performance over the 7-day application, combined with the good general and local tolerability and the need to apply the patches only once weekly confer to the new patches a favorable practicability for the long-term estrogen replacement therapy needed to control the most severe postmenopausal disorders.

Administration, Cutaneous↗

Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied.

Administration, Cutaneous↗

Design and evaluation of matrix diffusion controlled transdermal patches of verapamil hydrochloride.

Transdermal patches of verapamil hydrochloride were prepared using four different polymers (individual and combination): Eudragit RL100 (ERL100), Eudragit RS100 (ERS100), hydroxypropyl methylcellulose 15 cps (HPMC), and ethyl cellulose (EC), of varying degrees of hydrophilicity and hydrophobicity. The effect of the polymers on the technological properties, i.e., drug release, water vapor transmission rate (WVTR), and percentage moisture loss (ML), percentage moisture absorption (MA), folding endurance, and thickness, was investigated. Different formulations were prepared in accordance with the 2(3) factorial design, with ERL100 being the parent polymer. The patch containing ERL100 alone showed maximum WVTR, % MA, and % ML, which could be attributed to its hydrophilic nature. As expected, substitution with ERS100, HPMC, and EC decreased all the above values in accordance with their decreasing degree of hydrophilicity. In vitro release studies showed zero-order release of the drug from all the patches, and the mechanism of release was diffusion mediated. Moreover, the release of the drug was sustained and it extended over a period of 24 hr in all formulations. A12 emerged as the most satisfactory formulation insofar as its technological properties were concerned. Further, release and permeation of the drug from the most satisfactory formulation (A12) was evaluated through different biological barriers (shed snake skin, rabbit skin, and rat skin) to get an idea of the drug permeation through human skin. Shed snake's skin was found to be most permeable (82.56% drug release at 24 hr) and rat skin was least permeable (52.38%). Percutaneous absorption studies were carried out in rabbits. The pharmacokinetic parameters calculated from blood levels of the drug revealed a profile typical of a sustained release formulation, with the ability to maintain adequate plasma levels for 24 hr. [AUC: 3.09 mg/mL hr, Cmax: 203.95 microg/mL, Tmax: 8 hr]. It can therefore be concluded that the patch containing ERL100 and HPMC in the ratio 8:2 has achieved the objectives of transdermal drug delivery system, such as avoidance of first pass effect, extended release, and reduced frequency of administration.

Administration, Cutaneous↗

Detection of active tuberculosis by an MPB-64 transdermal patch: a field study.

The mycobacterial antigen MPB-64 was formulated for delivery in a transdermal patch and used as a diagnostic skin test reagent to detect active tuberculosis (TB) in patients attending a clinic in Manila, The Philippines. The MPB-64 Transdermal Patch was applied to 62 patients, 49 with sputum-positive active disease and 13 who had completed TB chemotherapy, and to 28 non-TB but tuberculin-positive controls. The results were read at 72 h. The sensitivity of the Transdermal Patch was 87.8%, with an efficacy of 92.9% and a specificity of 100%. The 13 TB patients who had completed 6 months of TB chemotherapy showed different reactions to the MPB64 patch test: those who had completed chemotherapy < 4 months before testing were positive; 50% of patients who completed chemotherapy 5 months previously were positive; and those who had completed chemotherapy 7 and 8 months before were negative. All the non-TB controls with positive tuberculin tests were negative to the MPB-64 Transdermal Patch, even at the highest protein dose tested. This test may be a useful method to distinguish active TB patients from TB-infected but asymptomatic individuals. Moreover, the MPB64 Transdermal Patch may be useful to monitor successful chemotherapy.

Antigens, Bacterial↗

Care of the dying: is pain control compromised or enhanced by continuation of the fentanyl transdermal patch in the dying phase?

The introduction of fentanyl transdermal patches has led to concern and confusion regarding the management of pain control in the dying phase. Data were collected retrospectively from 94 dying patients. Two groups were identified-patients treated with fentanyl transdermal patch who remained on the patch in the dying phase and patients on oral morphine who converted to a 24-hour subcutaneous infusion of diamorphine via a syringe driver in the dying phase. Both the fentanyl group and the diamorphine group had good pain control in the last 48 hours of life. During the last 48 hours of life, the proportion of patients with controlled pain was statistically significant in favor of the fentanyl group in 2 of the 12 observations undertaken, in particular whether the fentanyl transdermal patch should be continued or discontinued. Patients in the fentanyl group received fewer "as required" opioid doses compared to patients in the diamorphine group, although the difference was statistically significant only for the last day of life. This study showed that pain control was not compromised in the dying phase with continued use of the fentanyl patch.

Administration, Cutaneous↗

Adhesive backing foil interactions affecting the elasticity, adhesion strength of laminates, and how to interpret these properties of branded transdermal patches.

Standard tensile strength and peel adhesion tests were carried out to investigate interactions of pressure-sensitive adhesives (PSAs) with several backing foils used for transdermal patches. Seven branded transdermal patches (Alora, Cutanum, Estraderm MX 50, Estraderm TTS 50, Fem7 -50 micrograms, Menorest, Oesclim) were included in the investigation. Their skin adhesion measured in several clinical trials was compared with the results of the laboratory measurements according to PSTC-1 (Peel Adhesion for Single Coated Tapes 180 degrees Angle, Pressure Sensitive Tape Council, Illinois, 1996), such as Young's modulus at 3% elongation and peel adhesion to stainless steel. Data obtained for the PSA-coated backings (laminates) show increasing elasticity with increasing PSA thickness. Interactions of PSAs with backing foil became evident in significant changes in Young's modulus by low PSA thickness, as seen for the silicone adhesive. The Young's moduli of the laminates were found to be influenced not only by the elasticity of the backing foil but also by the chemical structure of the PSA. There was no correlation between the elasticity and peel adhesion of both the laminates and the branded patches. Likewise, for the branded patches the peel adhesion to stainless steel does not correlate with skin adhesion values obtained from clinical trials. The Young's modulus of the branded patches was between 4 N/mm2 (Oesclim) and 501 N/mm2 (Fem7). For the branded transdermal patches no correlation was found between Young's modulus and both the peel force on stainless steel and the skin adhesion reported in studies.

Adhesives↗

Bioavailability of estradiol from two transdermal patches.

The bioavailability of estradiol (CAS 50-28-2; E2) from a new "matrix type" estradiol transdermal patch (Dermestril; Test patch) was compared to that of the widely used "liquid-reservoir, membrane-controlled type" transdermal patch (Reference patch) in a two-way randomized cross-over study on 28 healthy postmenopausal women, during a single 4-day application of 2 patches (total content 8 mg E2, total nominal release rate 100 micrograms E2 in 24 h). Evaluated from the AUC0-96h, the extent of bioavailability was practically the same for the two patch types. Conversely the rate of bioavailability was significantly different, because from the Reference patch the release rate is fast in the first 24 h, leading to an E2 peak at 8 h and to a Cmax in average at 23 h. But after the 2nd day the release/absorption rate declines markedly, leading to E2 serum concentrations at the 3rd and 4th days possibly below the effective threshold. From the Test patch the release/absorption rate of E2 is more constant, leading to sustained E2 concentrations during the 4 days of application, with smaller fluctuations than during application of the Reference patch. In conclusion the Test patch can be considered practically bioequivalent to the Reference patch with regard to the extent of absorption, but not with regard to the rate of absorption, because the E2 concentrations in serum are more constant during the application of the Test transdermal patch than during the application of the Reference.

Administration, Cutaneous↗

Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia.

OBJECTIVE: Schizophrenic patients have high rates of cigarette smoking. The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications. METHOD: Forty-five subjects were randomly assigned to 1) the group therapy program of the American Lung Association (N=17) or 2) a specialized group therapy program for smokers with schizophrenia (N=28) that emphasized motivational enhancement, relapse prevention, social skills training, and psychoeducation. All subjects participated in 10 weeks of treatment with the nicotine transdermal patch (21 mg/day) and 10 weekly group therapy sessions and continued to receive their prestudy atypical (N=18) or typical (N=27) antipsychotic medications. Outcome variables included treatment retention, rate of smoking abstinence, and expired-breath carbon monoxide level. RESULTS: Smoking abstinence rates did not differ in the two group therapy programs. However, atypical antipsychotic agents, in combination with the nicotine transdermal patch, significantly enhanced the rate of smoking cessation (55.6% in the atypical agent group versus 22.2% in the typical group), which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels. Risperidone and olanzapine were associated with the highest quit rates. CONCLUSIONS: The results suggest that 1) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia, 2) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation, and 3) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia.

Administration, Cutaneous↗

Oestrogen transdermal patches for post partum depression in lactating mothers--a case report.

Oestrogen transdermal patches are now being used in the prophylaxis and treatment of post partum depression. Oestrogens are known to have potential adverse effects on breastfed infants. This case describes jaundice and poor weight gain in the child of a lactating mother prescribed oestrogen transdermal patches. There is a need for caution in the use of this therapy in breast feeding mothers and health professionals should be alert for problems.

Administration, Cutaneous↗

Efficacy on climacteric symptoms of a new estradiol transdermal patch with active matrix in comparison with a reference reservoir patch. Two long-term randomized multicenter parallel-group studies.

METHODS: Two randomized prospective multicentre parallel group studies were performed (one in Germany and the other in Italy) in symptomatic postmenopausal women. The goal was to assess the efficacy on climacteric symptoms and the safety of a new estradiol (CAS 50-28-2) transdermal patch with solid active matrix (SAM) in comparison to a conventional liquid reservoir (LR) type estradiol transdermal patch. Both patches released 50 micrograms/day estradiol. One group of patients received the SAM patch and the other the LR patch in 4-week cycles, with a twice-weekly application of the patches for 3 weeks, followed by one week without patches. Progestin opposition was achieved with medroxyprogesterone acetate 5 mg/day orally in the last 11 days of patch application in the German study and with 10 mg/day in the last 12 days of patch application in the Italian study. Both studies were divided into two Parts: Part 1 with three 4-week cycles for a total of 12 weeks and Part 2 for other ten 4-weeks cycles in which the patches could be applied also continuously. The total duration of the study was therefore 52 weeks. RESULTS: Germany study. 133 patients resulted randomized to the SAM group and 129 to the LR group. Both estradiol patches quickly relieved climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the Kupperman Index. At the end of Part 1, in the SAM group 91% and in the LR group 96% of patients reported relief from climacteric symptoms. At the end of Part 2 the percentages were 98% and 95%, respectively. The two patches were therapeutically equivalent with a power greater than 99.7%. Both patches were systemically fairly well tolerated. Only 4.5% of patients in the SAM group and 3.9% in the LR group discontinued prematurely for possible adverse reactions related to estradiol. There was no significant difference between the two patches with regard to systemic tolerability. Conversely, with regard to local skin reactions, the SAM patch was significantly (p < 0.01) better tolerated than the LR patch. The adhesion to the skin of the SAM patches was better than that of the LR patches. RESULTS. Italian study. 139 patients resulted randomized to the SAM patch and 128 to the LR patch. Also in this study both types of patches relieved the climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the visual analogue scale (VAS) recordings of severity of hot flushes and of sweats. At the end of Part 1 both patches relieved 95% of patients from climacteric symptoms. At the end of Part 2, i.e. after 52 weeks, 100% of patients were relieved from climacteric symptoms. Of these, 72% in the SAM group and 78% in the LR group reported complete disappearance of symptoms. Also in the Italian study, therefore, the two patches were found therapeutically equivalent. Both patches stopped or even reversed bone mineral loss in L2-L4 and had some favorable effects on lipid metabolism. Both patches were systemically equally fairly well tolerated with premature discontinuations for systemic adverse drug reactions in only 5.0% of patients in the SAM group and 3.9% in the LR group. Conversely, as in the German study, the SAM patches were significantly better tolerated by the skin (p < 0.0001). CONCLUSIONS: The two types of estradiol transdermal patches were equivalent in providing an effective and rapid relief from climacteric symptoms. Systemically both patches were fairly well tolerated. The SAM patches were significantly better tolerated by the skin. The better local tolerability combined with better adhesion and cosmetic properties render the SAM patches very patient friendly and improve the compliance in the long term estrogen replacement therapy required to reduce osteoporosis and cardiovascular risks.

Adhesiveness↗

Potential and problems of developing transdermal patches for veterinary applications.

A new frontier in the administration of therapeutic drugs to veterinary species is transdermal drug delivery. The primary challenge in developing these systems is rooted in the wide differences in skin structure and function seen in species ranging from cats to cows. The efficacy of a transdermal system is primarily dependent upon the barrier properties of the targeted species skin, as well as the ratio of the area of the transdermal patch to the species total body mass needed to achieve effective systemic drug concentrations. A drug must have sufficient lipid solubility to traverse the epidermal barrier to be considered for delivery for this route. A number of insecticides have been developed in liquid "pour-on" formulations that illustrate the efficacy of this route of administration for veterinary species. The human transdermal fentanyl patch has been successfully used in cats and dogs for post-operative analgesia. The future development of transdermal drug delivery systems for veterinary species will be drug and species specific. With efficient experimental designs and available transdermal patch technology, there are no obvious hurdles to the development of effective systems in many veterinary species.

Administration, Cutaneous↗

Development and evaluation of transdermal patches of nonivamide and sodium nonivamide acetate.

Transdermal patches were developed and evaluated for two synthetic derivatives of capsaicin, nonivamide (NVA) and sodium nonivamide acetate (SNA), by in vitro and in vivo skin permeation. The designed system was essentially based on natural rubber or polymeric Gelva dispersion. The characterization of physicochemical properties of the patches showed adequate adhesive force and low thickness which suggested these patch formulations possessed good quality. In the study of in vitro percutaneous experiment, the predicted therapeutic activities of patches were all higher than that of a commercially available plaster after the calculation of antinociceptive index. The highest in vitro penetration flux was found in the Gelva patch for NVA. The result of in vivo experiments revealed a high obverse correlation with that of in vitro experiments. The information of this present study is helpful for the further development of NVA and SNA transdermal drug delivery system.

Administration, Cutaneous↗

Alternatives to oral estrogen replacement. Transdermal patches, percutaneous gels, vaginal creams and rings, implants, other methods of delivery.

Alternatives to oral estrogen replacement, including the transdermal patch, deliver estradiol in a constant manner, produce more physiologic estrone and estradiol levels than oral therapy, and avoid the first-pass effect on hepatic protein synthesis. Transdermal patches and estradiol implants have been demonstrated to produce favorable lipid profiles, prevent bone loss, relieve vasomotor symptoms, and improve urogenital atrophy. Vaginal estrogen is an effective treatment for vaginal atrophy. The advantages and disadvantages of each of the hormonal alternatives to oral estrogen replacement are discussed.

Administration, Cutaneous↗

Pharmacokinetics of estradiol and of estrone during application of a new 7-day estradiol transdermal patch with active matrix.

The pharmacokinetic patterns of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) were investigated in 18 women in natural or surgical menopause during the application of a new estradiol transdermal patch with active matrix and without absorption enhancers designed for epicutaneous applications of 7 days (hereinafter called "patch 7D"). The study was made with randomized and balanced sequences of applications in cross-over of either patch 7D or of an authorized estradiol transdermal patch with a nominal release rate of 50 micrograms/day estradiol designed for a twice-a-week epicutaneous application (hereinafter called "patch 50"). The sequences consisted of applications for 3 weeks either of 3 patches 7D or of 6 patches 50. The patches were applied on the skin of the hips or upper buttocks. The serum samples were obtained during the 1st and during the last week of application of the patches. Estradiol (E2) was assayed in serum by a double-antibody RIA method selective for free estradiol. Estrone (E1) was assayed in serum using a 3H-estrone RIA method. The steady state with regard to E2 and E1 was achieved already during the application of the 2nd patch. Patch 7D provided within 6 h an increase of the E2 concentrations in serum from the basal postmenopausal level of less than 3 pg/ml to therapeutically effective concentrations. The Cmax of E2 of 45 pg/ml was reached on average after 25 h, the concentrations of E2 remaining at sustained and therapeutically effective levels during the whole application of patch 7D. At steady state, during the 3rd week of application, the Cav was on average 31 pg/ml. With a small delay, E1 also increased from the basal 15 pg/ml to a Cmax of 41 pg/ml after 44 h. At steady state, during the 3rd week of application, the Cav was on average 38 pg/ml. Patch 7D provided a similar bioavailability as patch 50 with regard to the rate and the extent of absorption of E2, as shown by the AUCs during the 7-day applications of one patch 7D compared to those during the 7-day applications of 2 patches 50. The release of E2 from patch 7D is therefore similar to that of patch 50, i.e. on an average of 50 micrograms/day over a 7-day period of application. The E2/E1 ratio increased from the postmenopausal values lower than 0.2 found before the application of patch 7D to average values of 0.67, i.e., to values that are normally found during the fertile life of the woman. The improvement of the E2/E1 ratio occurred already in the first 6-12 h of application of patch 7D. The E2/E1 ratio returned rapidly to the initial low postmenopausal levels after removal of the patch. Patch 7D was well tolerated by the skin, probably because it does not contain absorption enhancers. It provoked, however, some systemic adverse reactions typical of E2 overdosing. In the therapeutic practice these adverse reactions can easily be avoided using patches 7D of lower strength. No drop-out due to systemic or local intolerance occurred. The adhesion of patch 7D on the skin was good. During the application of a total of 54 patches, only in one occasion one patch became partially detached (about 40% of the total area) from the 3rd to the 7th day during the first 7-day period of application.

Administration, Cutaneous↗

Cost analysis of once-daily ISMN versus twice-daily ISMN or transdermal patch for nitrate prophylaxis.

OBJECTIVE: To compare the costs and outcomes of treating exercise-induced angina with once- or twice-daily isosorbide mononitrate (ISMN) or transdermal patch. METHOD: A decision-analytic model was designed based on published literature showing compliance and increasing symptoms and estimates from physicians on treatment patterns and worsening symptoms. RESULTS: Data show that patients are more compliant with once-daily ISMN (Imdur, Astra Hässle, Mölndal, Sweden) and patch regimens than with twice-daily dose. Based upon the assumption that more compliant patients are better controlled, the model found that fewer medical care resources were consumed by patients treated with the once-daily and the patch regimens. The unit cost of the twice-daily ISMN regimen is 40% of the unit cost of the once-daily. Annual costs of treating an exercise-induced angina patient are 248 pounds for Imdur compared to 250 pounds for the twice-daily ISMN and 299 pounds for the transdermal patch. CONCLUSION: Unit prices alone are not good indicators for estimating medical management costs.

Administration, Cutaneous↗

Assessment of skin safety of a new glyceryl trinitrate transdermal patch. Animal and human studies.

The experimental models and the studies in man employed to assess the skin and general safety of a newly developed glyceryl trinitrate (GTN, CAS 55-63-0) transdermal patch, hereinafter coded EPI, are described. EPI was found well tolerated by the skin after single or 28-day repeated epicutaneous application on the rabbit, devoid of phototoxicity in the mouse, devoid of skin sensitizing potential in the guinea pig and devoid of photosensitizing effects in the guinea pig. Tested were also, with negative results, the cytotoxic, hemolytic and genotoxic potential, the presence of bacterial endotoxins, the systemic and intracutaneous toxicity, and the possible conjunctival irritant effects. The application of EPI for 14 consecutive days on the thoracic skin of 28 healthy volunteers did not provoke subjective discomfort such as itching, burning or pain, or objective skin lesions. On the application site a light and transient erythema was often found demonstrating the transcutaneous absorption of the vasodilating GTN from the patch. The 14-day application was followed after two weeks by the application of a challenge EPI patch to detect a possible skin sensitization by EPI. No skin reaction was elicited, showing that also in man EPI is devoid of skin sensitizing potential. During the 14-day application of EPI several GTN commonly induced systemic adverse reactions were observed, particularly headache, confirming the systemic bioavailability of GTN from the patch. Headache rapidly disappeared after removal of the patch, in parallel with the decrease of the blood concentrations of GTN and of its active metabolites, consistently with the previous pharmacokinetic findings. This is an advantage of the administration of GTN with the transdermal patch because, in the case of unbearable headache, the patient is relieved by the simple removal of the patch.

Adhesives↗

Clonidine transdermal patch poisoning.

A case of infant clonidine poisoning from a transdermal patch that had been worn for five days by an adult and then discarded is described. The infant became hypotensive with a systolic blood pressure of 38 mm Hg, and a dopamine infusion was required for six hours to maintain adequate blood pressure. The infant was discharged 24 hours after admission. Clonidine toxicity, transdermal delivery system pharmacokinetics, and poison prevention are discussed.

Accidents, Home↗