THE RESPIRATORY EFFECTS OF A POTENT ANALGESIC (GPA 2087) IN MAN

The respiratory depressant effects of a potent analgesic (GPA2087) were compared with morphine in a randomized double-blindcross-over study in human volunteers. Using a rebreathing technique,carbon dioxide response curves were plotted automatically witha special-purpose analog computer. The respiratory depressantrelative potency of GPA 2087 to morphine was found to be 1.21with lower and upper 95 per cent confidence limits of 0.88 and2.04. Our best estimate based on the displacement of the respiratoryresponse curve is that GPA 2087 8 mg is the equivalent of morphine10 mg in our population of volunteers. ^*Geigy Pharmaceuticals, Ardsley, New York, U.S.A. ^*Present address: Salisbury General Infirmary, Odstock Branch,Salisbury, Wiltshire, England.     

The Standardized Normal Ivy Bleeding Time and Its Prolongation by Aspirin

A standardized, reproducible Ivy bleeding time technic has been describedwhich permits one to obtain accurate bleeding time data in man. Thetechnic was used to standardize an aspirin tolerance test in which 60 normal males had a control bleeding time; were given, on a double blind basis,either placebo or 1 Gm. of aspirin, and had a second bleeding time 2 hourslater. The control values were: mean, 5 min.; mean ± 2 st. dev., 2 min.,30 sec. to 10 min. The values after placebo were: mean, 5 min., 30 sec.;mean ± 2 st. dev., 2 min., 30 sec. to 11 min. The values after aspirin were:mean, 9 min., 30 sec.; mean ± 2 st. dev., 4 min. to 21 min. The differencebetween the mean bleeding time after placebo and after aspirin was highlysignificant (p < 0.001). The distribution of the bleeding times after aspirinsuggested that normal subjects do not respond to aspirin as a single population. The degree of prolongation of the bleeding time and the large size ofthe drops of blood observed in some subjects suggested to us that smallamounts of aspirin may exert a significant effect upon hemostasis in normalindividuals.

Submitted on January 10, 1969 Accepted on April 23, 1969     

Misleading high tobramycin plasma concentrations can be caused by skin contamination of fingerprick blood following inhalation of nebulized tobramycin (TOBI): a short report

We observed unexpected high plasma concentrations of tobramycin (48.5 and 28.1 mg/L) in fingerprick blood samples after the nebulization of tobramycin solution for inhalation (tobramycin 300 mg/5 mL, TOBI by 2 young children aged 3 years. To investigate whether dermal contamination could be the source of error, 3 adult volunteers were present during another nebulization by a third child (age 2 years). The volunteers had exposure to tobramycin by handling the nebulizer or the nebule and also by inhalation from holding the child and being in close proximity while TOBI was being administered. Five blood samples by fingerprick and 2 by venipuncture were collected and assayed for tobramycin concentration. On each occasion the site was swabbed with alcohol wipes to mimic standard patient sampling methods. One site was resampled after cleaning of hands with 2% chlorhexidine gluconate and water. Tobramycin concentrations from venipuncture 1-2 hours after nebulization were all <0.2 mg/L except for 1 result of 1.2 mg/L. The tobramycin concentrations from fingerpricks before hand washing varied between 6.8 and 172 mg/L, and after hand washing between 0.3 and 17.6 mg/L. Contamination of fingers with tobramycin is likely to have caused the error in the 2 initial cases and did cause misleadingly elevated levels in the adult volunteers. We caution that therapeutic drug monitoring of nebulized tobramycin should not be done by fingerprick sampling, and care should be taken to avoid contamination of the venipuncture site.