No abstract

Twenty-seven healthy male volunteers participated in a double-blind, five-way crossover designed comparison of the new, selective H,-receptor antagonist cetirizine (10 mg q.d.) and terfenadine (60 mg b i d . and 120 mg q.d.) versus the older H,-receptor antagonist triprolidine ( 5 mg b.i.d.) and placebo.Medication was administered during four consecutive days. Subjects were tested on the 1st and 4th treatment day. On each test day subjects drove an instrumented vehicle over a 100 km highway circuit while attempting to maintain a constant speed (90 k d h r ) and a steady lateral position within the right traffic lane. Thereafter they performed three computerized memory tasks. On the 4th treatment day, sleep latency was measured before and after the driving test. On both days, triprolidine significantly impaired performance in the driving and psychometric tests. Triprolidine also significantly reduced sleep latency in comparison to placebo on the 4th treatment day. Terfenadine 60 mg b.i.d. impaired psychometric performance after subchronic treatment.It was concluded that cetirizine, like terfenadine, belongs to the newer class of antihistamines and can be safely used by patients who continue their daily activities.

Carboplatin is a chemotherapeutic agent frequently used in the treatment of various malignancies. An individual dosing strategy has been recommended to yield the most optimal exposure, expressed as the area under the concentration-time curve (AUC). The formula developed by Calvert et al. (dose = target-AUC x [GFR + 25]) can be used to achieve this. However, due to the inconvenient [51Cr]-ethylenediamine-tetraacetic acid ([51Cr]-EDTA)-based measurement of the glomerular filtration rate (GFR), its application in the clinic has thus far been limited. Chatelut and co-workers have recently proposed a formula to estimate carboplatin clearance using the serum creatinine concentration. We retrospectively tested the Chatelut equation and the Calvert formula using either the creatinine clearance based on 24-h urine collection or the creatinine clearance based on the formula of Cockcroft and Gault. The latter equations were shown to predict the carboplatin clearance reasonably well, although systematic overprediction and underprediction occurred. However, the formula proposed by Chatelut and co-workers had no significant bias and was precise. It is proposed that this formula be used to calculate the optimal carboplatin dosage after prospective validation has been performed.

The recommended dose for phase II studies is 8.4 mg/m2 when administered as a 24-hour infusion, which is well tolerated. Further studies will be necessary to account for the putative nonlinear behavior of the drug.