Ketamine is known to provide analgesic effects without an anesthetic when administered in a low dose. We previously reported that a tablet containing ketamine had analgesic effects in patients with neuropathic pain. In the present study, we compared the plasma concentration profiles of the enantiomers of ketamine and its active metabolite, norketamine, up to 8 h after the administration of 20 mg of ketamine by injection, after the administration of two tablets containing 25 mg of ketamine, after the administration of two sublingual tablets containing 25 mg of ketamine, after the insertion of a suppository containing 50 mg of ketamine, and after the application of a nasal spray containing 25 mg of ketamine to three healthy volunteers. The plasma concentration of ketamine biexponentially declined after the administration by injection; the value of T(1/2beta) for ketamine was approximately 120 min. The bioavailability of the tablet was estimated to be approximately 20%; the area under the plasma concentration-time curve, (AUC)(0-->8 h), of norketamine was approximately 500 ng h/ml in both enantiomers. The bioavailabilities of the sublingual tablet and the suppository were estimated to both be approximately 30%; the AUC(0-->8 h) of norketamine was 280-460 ng h/ml in both enantiomers. The plasma concentration profiles of the sublingual tablet and the suppository were almost similar to that of the tablet. The bioavailability of the nasal spray was estimated to be approximately 45%, which was the highest value among the preparations tested, and the AUC(0-->6 h) of norketamine was low (approximately 100 ng h/ml) in both enantiomers. These pharmacokinetic findings suggested that all of the ketamine preparations tested in this study may be useful for the alleviation of neuropathic pain. We propose that the type of ketamine preparation should be selected in accordance with the patient's disease condition and the required dosage amount of ketamine.

Although a variety of topical treatments have been used for skin hyperpigmentation, the effectiveness of each varies after prolonged treatment. In this study, 136 Oriental patients who were followed up for more than 12 weeks were analyzed. The treatment protocol was composed of two steps: bleaching (2 to 6 weeks) and healing (2 to 6 weeks); 0.1% to 0.4% all-trans retinoic acid aqueous gel was originally prepared and applied concomitantly with hydroquinone-lactic acid ointment for bleaching. After obtaining sufficient improvement of the hyperpigmentation, a corticosteroid was applied topically with hydroquinone and ascorbic acid for healing. Improvement was evaluated with a narrow-band reflectance spectrophotometer. The results were successful in more than 80 percent of cases of senile lentigines and postinflammatory hyperpigmentations, especially on the face. Sixty percent of cases of nevus spilus were also successfully treated. Although the transient adverse effects of this treatment may be more severe than conventional treatment, this strong bleaching protocol improves a variety of hyperpigmented lesions, including nevus spilus, with a higher success rate and a shorter treatment period than conventional protocols.

QSR laser combined with the topical bleaching pretreatment appeared to treat ADM consistently with a low occurrence rate of PIH and lessen the number of laser sessions and total treatment period and may also be applied to any other lesions with both epidermal and dermal pigmentation.

We have studied the pharmacokinetics of methylphenidate enantiomers after the oral administration of different doses of racemic methylphenidate to one patient with narcolepsy and to four healthy volunteers. The plasma concentrations of (+)-methylphenidate were much higher than those of (-)-methylphenidate after each dose in all subjects. In the patient the oral clearance (CL/f) of (+)-methylphenidate fell 3-fold and the area under the concentration-time curve (AUC) rose 7-fold when the dose was increased from 20 to 40 mg (from 0.27 to 0.53 mg.kg-1), in spite of the relatively constant terminal half-life of 2.6-2.7 h. Similar dose-dependency was also observed in the healthy volunteers in the dose range of 10-60 mg (0.12-0.77 mg.kg-1). The mean value of CL/f for the 40 mg dose was significantly lower than that for the 20 mg dose. The mean AUC of the (+)-isomer corrected to a dose of 10 mg increased significantly between the 20 mg and 40 mg doses. In the urine (+)- and (-)-ritalinic acid were excreted for 48 h after each dose as 32-37% and 34-40% of the dose respectively. The mean total recoveries (sum of enantiomers of methylphenidate and its metabolite, ritalinic acid) in the urine were relatively constant (63-78% of the doses), suggesting that the changes in AUC with dose may not be due to a change in the intestinal absorption of racemic methylphenidate. We conclude that the nonlinear kinetics of (+)-methylphenidate may be due to saturation of its presystemic elimination.