A long-term cross-over pharmacokinetic study comparing perphenazine decanoate and haloperidol decanoate in schizophrenic patients.

The purpose of the study was to investigate clinical and pharmacokinetic parameters concerning perphenazine decanoate (PD) and haloperidol decanoate (HD) with an interval of 3 weeks during a study period of 51 weeks. This was done by using the available drug preparations in chronic schizophrenic patients in a randomised, double-blind, cross-over, multicentre study. In addition, an elimination phase of 6 weeks was added, when no IM injections of the depot drugs were given. Twenty-nine patients in a stable neuroleptic maintenance phase entered the study. The patients were rated during the trial according to the CPRS-SCHZ and CGI scales, the UKU side effect scale and serum concentrations of the drugs and prolactin were monitored. There was no significant difference between the drugs in antipsychotic efficacy or side effects. Thus, the doses were equipotent with regard to the CPRS-SCHZ scores. However, the patients' global improvement rating was higher for PD (52%) than for HD (39%) (P > 0.05). The elimination of both drugs was very slow. No interaction effects between PD and HD were observed. The serum levels of HD were in most patients lower than those recommended for acute-subacute treatment. The mean doses were 117 mg (0.29 mmol), range 20-313 mg PD and 120 mg (0.32 mmol), range 20-350 mg HD. The serum concentrations in nmol/L of perphenazine and haloperidol (week 24) were 0.8-15.9 and 2.3-46.7, respectively.

Inhibitory effect of loratadine and clemastine on histamine release in human skin.

The inhibitory effect of the two H1 antagonists clemastine and loratadine on histamine release in human skin was studied in 15 volunteers. The antihistamines and placebo were administered orally (clemastine 2 mg twice a day, loratadine 10 mg once a day) for 5 days according to a double-blind, crossover design. Clemastine caused a significant sedation in comparison with placebo, whereas there was no difference between loratadine and placebo in this respect. After 5 days' medication, flare reaction was induced by intradermal injection of histamine and the histamine liberator compound 48/80. The antihistamine dosages were approximately equipotent and inhibited the flare response induced by histamine to about the same extent, whereas the flares induced by compound 48/80 were still more inhibited by both drugs. The results indicate that clemastine and loratadine not only inhibit histamine effects at H1 receptor level, but have additional suppressive effects, probably due to inhibition of mast cell degranulation. The simple, virtually noninvasive, in vivo technique described in this paper does not require chemical analysis of the released mediators and could be used to screen 'mast cell stabilizing' effects of various antihistamines.