Bioequivalence of clozapine orally disintegrating 100-mg tablets compared with clozapine solid oral 100-mg tablets after multiple doses in patients with schizophrenia.

BACKGROUND: This study compared the bioequivalence of FazaClo (clozapine orally disintegrating tablets) 100 mg to Clozaril (clozapine standard oral tablets) 100 mg after multiple doses in patients with schizophrenia. METHODS: This was a randomized, open-label, multiple-dose study in which patients with schizophrenia received FazaClo or Clozaril 100 mg twice daily for 5 days before crossing over to the alternate therapy. Blood samples were obtained at regular intervals during and after the completion of treatment, and standard pharmacokinetic parameters were calculated. Safety and patient satisfaction with FazaClo were also assessed. RESULTS: Thirty-six patients were enrolled, of whom 33 completed the study and 30 were included in the steady-state analyses. All pharmacokinetic parameters for clozapine and desmethylclozapine (the major metabolite of clozapine) were similar between FazaClo and Clozaril in both the completer and steady-state populations. Geometric mean values for steady-state maximum and minimum concentrations and area under the plasma concentration-time curve for FazaClo were all within 95-105% of those for Clozarilwell within the range considered by the US FDA as acceptable for bioequivalence (80-125%). Patients also expressed a high level of satisfaction with the FazaClo orally disintegrating tablet formulation. CONCLUSIONS: FazaClo produced pharmacokinetic profiles almost identical to those of Clozaril. This should provide clinicians with reassurance that patients who receive FazaClo will achieve plasma drug concentrations similar to those produced by the same daily dose of Clozaril, and that no cross-titration is necessary when switching from one of these clozapine formulations to the other.

Psychotropic drugs use and risk of heat-related hospitalisation.

OBJECTIVE: To assess if use of psychotropic drugs is associated with an increased risk of admission for heat-related pathologies during a heat wave period. METHOD: We conducted a matched case-control study. Cases were defined as subjects admitted to an emergency department for heat-related pathology (hyperthermia or heat stroke) over the August 2003 heat wave. Controls were defined as subjects living in the same area but not hospitalised over the same period and who had at least one prescription form submitted for refunding by the social security insurance in July 2003. Multivariate analyses were used to identify psychotropic drugs independently associated with hospital referral during the heat wave period. RESULTS: Out of the 1405 patients admitted to the emergency department, 56 (4%) presented with heat-related pathology. The mean age of cases was 83 years. Multivariate analyses showed that cases were more likely than controls to be treated with anticholinergic drugs (OR 6.0, 95% CI 1.8-19.6), antipsychotics (OR 4.6, 95% CI 1.9-11.2) or anxiolytics (OR 2.4, 95% CI 1.3-4.4). CONCLUSION: In special risk situations such as heat waves, the risk/benefit ratio of psychotropic drugs which could interfere with body temperature regulation has to be carefully assessed, particularly in the elderly.

Assessment of the use of sialogogues in the clinical management of patients with xerostomia.

This study was conducted to assess the clinical efficacy and adverse effects of pilocarpine, bethanechol and cevimeline in patients with xerostomia. In this open-label crossover assessment in 20 patients with xerostomia, a one- to two-week course of each medication with a one-week washout period was prescribed. Side effects, symptoms, whole stimulated and unstimulated saliva were measured. Each sialogogue was found to increase saliva and decrease symptoms. A mixed-effects analysis showed a greater increase in stimulated saliva on bethanechol compared to pilocarpine (0.106, p = 0.0272). Increased sweating was the most common side effect, experienced more frequently with pilocarpine as compared to bethanechol (p = 0.0588) or cevimeline (p = 0.0143). A carryover effect beyond the washout period was seen. Effects on saliva and side effects vary between sialogogues, suggesting a benefit of trials with different sialogogues to determine individual patient preference. The observed carryover effect suggests that intermittent treatment may be an alternative to continuous treatment with sialogogues.

Bedside assessment of sympathetic skin response after spinal cord injury: a brief report comparing inspiratory gasp and visual stimulus.

STUDY DESIGN: A case control study in five controls, and 20 tetraplegic and paraplegic patients, complete and incomplete. OBJECTIVE: The aim was to assess the feasibility of a simple test for sympathetic system preservation after spinal cord damage in a pain-free manner and which could be undertaken worldwide without specialist equipment or manpower. SETTINGS: Patients were attending the Southport Regional Spinal Injuries Centre, England, either as outpatients or as in-patients during rehabilitation. METHODS: The sympathetic skin response (SSR) was recorded on a single-channel ECG recorder from the right hand and right foot in turn after inspiratory gasp (IG) or visual stimulation. RESULTS: Unlike the visually evoked SSR, the gasp-evoked SSR was reliable, albeit of variable amplitude, and there was little difference between the hand and foot. Paraplegics had similar SSRs in the hands as the controls. There was minor insignificant habituation of response for the gasp reflex. There was occasional unexpected SSR distally in patients with complete lesions, and in patients with incomplete lesions the responses could not have been predicted from the sensory motor pattern. CONCLUSIONS: Trained IG induces an SSR which is sufficient to elucidate sympathetic loss following spinal cord injury. It is superior to visual stimulation in this respect. Habituation is not a problem with at least 1 min between tests, and high doses of anticholinergics agents may impair the response.

EEMCO guidance for the efficacy assessment of antiperspirants and deodorants.

Overproduction of sweat, sweaty skin and body odours are unpleasant for many social groups. Body cleansing products are designed to combat these undesirable features of skin. In addition, antiperspirant and deodorant products are more specifically used in the underarm site by a large part of the adult population. Antiperspirants are offered to control emotionally triggered sweating in the armpit. Deodorants are designed to combat malodour generated from bacteria-modified sweat. This review summarizes the physiology of eccrine, apocrine and apoeccrine sweat glands. The mechanisms of action of antiperspirants and deodorants are described as well as the factors influencing their efficacies. A series of tests using various measurement methods can be used to demonstrate the efficacy of antiperspirants. These include the gravimetric method, water evaporation quantification, electrodermal measurements, staining procedures, dye injections and cyanoacrylate skin surface strippings and casting replicas. Deodorant efficacy can be evaluated by sensory assessments performed by an expert panel. Indirect support is provided by visualization of apocrine gland excretion and collection of sweat and volatile compounds. Microbiological assessments and chromatographic analysis also provide indirect information.

Assessment of the activity of antiperspirants added to surgical hand disinfectants: methodological aspects and first observations.

Due to the risk of sensitization caused by glove powder, the use of unpowdered latex gloves is increasing. These unpowdered gloves need a special inner-surface layer which makes it easier for the applicant to put the glove on the hand and to remove it again. However, many users report difficulties with removing the gloves because of sweat production within the glove. Therefore, a method has been developed to evaluate the efficacy of antiperspirants which may be added either to the inner-surface layer of the glove or to hand disinfectants or to skin-care products used before the gloves are put on. The paper describes various trials to optimize this method.

[Assessment of autonomic nervous function in impotence using sweat response induced by intradermal injection of acetylcholine].

It is important to evaluate the autonomic nervous function which controls penile erection. One method utilizes intradermal injection of acetylcholine to produce localized sweat response. The sweat response depends on the peripheral autonomic nervous supply. Therefore, the response can be used to detect peripheral autonomic nervous dysfunction. We tried to evaluate the peripheral autonomic dysfunction in 29 impotence using a sweat spots test. We classified the 29 impotence into 6 groups with standard tests such as the papaverine test, nocturnal penile tumescence monitoring, recordings of bulbocavernous reflex, etc. The results were as follows: psychogenic IMP; 8, neurogenic IMP; 8, arterial insufficiency; 5, corporeal veno-occlusive insufficiency; 6 neurogenic with arterial insufficiency; 1, and neurogenic with corporeal veno-occlusive insufficiency; 1. The score of sweat spots test was 25.3 +/- 10.9, being in normal, nineteen severe in 3 and slightly abnormal in 7. Many cases of severe and slightly abnormal patients were DM patients classified into neurogenic IMP. We found 2 cases that were not detected by bulbocavernous reflex but found to be abnormal by sweat spots test. Therefore we conclude that this test effective to detect the autonomic nervous dysfunction in impotence.

Assessment of basal and stimulated sweating in diabetes using a direct-reading computerized sudorometer.

Abnormalities of eccrine sweating are thought to be common in diabetes. We describe a ventilated-capsule sudorometer for the continuous measurement of basal and stimulated sweat secretion. It is sensitive (detecting as little as 200 ng water vapour), precise, and stable. Since it measures dewpoint rather than relative humidity, it can be calibrated to read sweat volumes directly and independently of ambient temperature and humidity. Preliminary studies using this technique show that basal skin water loss is significantly diminished in patients with established diabetic neuropathy (0.91 +/- 0.18 g (+/- SD) cm-2 h-1) compared with normal subjects (1.21 +/- 0.39 g cm-2 h-1; p = 0.04) and non-neuropathic diabetic subjects (1.32 +/- 0.48 g cm-2 h-1; p = 0.04), and that local sweating induced by iontophoresis of 10 g l-1 acetylcholine is significantly reduced in diabetic subjects up to 5 min of recording (0.95 +/- 0.43 vs 1.26 +/- 0.40 mg; p = 0.02). In neuropathic subjects both low- and high-amplitude responses are seen, the latter probably representing denervation supersensitivity. Further studies with sensitive sudorometry should enable the mechanisms of these abnormal responses to be established.