M.K. Aravind

Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy

We undertook a prospective study to evaluate the relationship between the onset and degree of sedation and the midazolam plasma concentration in children between 6 and 18 years of age during esophagogastroduodenoscopy. Thirteen boys and seven girls (median age 13.5 years) were studied. Midazolam was injected intravenously for 5 minutes, and the dose was titrated to sedation or a maximum dose of 0.1 mg/kg was given. Plasma midazolam concentration was determined just before and at 5, 10, 15, 30, 45, and 60 minutes after the start of midazolam injection. The patients level of sedation was evaluated by an assistant at each blood sampling time. Clearance, volume of distribution, and terminal elimination (beta) half-life were estimated from a biexponential fit of the serial plasma midazolam concentrations. Mean beta half-life of midazolam was 47 +/- 26 minutes and mean clearance was 10.0 +/- 5.0 ml/min per kilogram of body weight. Maximum level of sedation occurred at 5 minutes after initiation of the injection and corresponded to a mean peak midazolam serum concentration of 229 +/- 39 micrograms/L. Thereafter, a decline of mean sedation scores paralleled the decrease in midazolam concentration. Mean oxygen saturation remained greater than 94% during the study. We conclude that children metabolize and excrete midazolam more rapidly than adults do and that sedation adequate for endoscopy is safely achieved in the majority of children with a midazolam dose of 0.05 to 0.1 mg/kg and a mean peak midazolam concentration greater than 200 microgram/L.

Enantiomer‐selective pharmacokinetics and metabolism of ketorolac in children

To compare the pharmacokinetics and metabolism of R (+)‐ and S (−)‐ ketorolac in children.

Analysis of caffeine: comparison of the manual enzyme multiplied immunoassay (EMIT), automated EMIT, and high-performance liquid chromatography procedures.

Summary: Caffeine has been recommended for the treatment of apnea in newborn children. Most of the current methods for measurement of caffeine in newborns have used high-performance liquid chromatography (HPLC) because analysis can be performed on as little as 50 μl of serum, an important factor when obtaining multiple blood samples for routine drug monitoring in infants and children. We evaluated the manual Syva enzyme multiplied immunoassay technique (EMIT) caffeine procedure and compared the assay results with our HPLC caffeine method. The EMIT procedure was also automated, and these results were compared with those of the manual and HPLC procedures. The 7-μg/ml calibrator was analyzed 20 times to establsh withinrun precision for the manual procedure. The mean ± SD was 6.97 ± 0.33, and the coefficient of variation (CV) was 4.80%. Reproducibility was tested by multiple analysis of the 11-μg/ml control. The mean ± SD (CV) for the manual system was 11.3 ± 0.45 (4%), n = 17; for the HPLC system, 10.58 ± 0.89 (8.4%), n = 10; and for the automated system, 10.4 ± 0.78 (7.5%), n = 12. Samples from 32 patients were analyzed by each of the above procedures. There was a good correlation among all three procedures. The correlation coefficient (r) for HPLC vs. manual EMIT was 0.98; for HPLC vs. automated EMIT, 0.97; and for automated EMIT vs. manual EMIT, 0.96. We conclude that the new Syva EMIT caffeine method is reliable and reproducible and can be applied to automated analysis. Serum caffeine levels greater than 30 μg/ml require dilution when analyzed by either EMIT procedure. We have found that serum levels greater than this value may be required to prevent apnea in some children.

Determination of Ticarcillin in Serum by Reversed Phase High Performance Liquid Chromatography

Abstract Ticarcillin is a semi-synthetic penicillin useful against several Pseudomonas species. In order to easily quantitate this drug, a new procedure was developed whereby ticarcillin in serum is converted to its free acid form by the addition of citric acid and, subsequently, extracted into ethyl acetate. The organic extract which contains the nonionized form of ticarcillin is dried under nitrogen, the sample is reconstituted with mobile phase and analyzed by high performance liquid chromatography. Elution is completed in less than five minutes. The assay is linear from 1 mg/L through 100 mg/L. The correlation coefficient of ticarcillin concentration to peak area (r) was 0. 999 over this concentration range. The small sample volume (100 yl) makes this assay particularly suitable for pediatric patients.

Physicochemical Factors on The Hydrolysis of Dipyrone

Clinical Pharmacology & Therapeutics (2003) 73, P49–P49; doi:

KETOROLAC (+)R AND (-)S STEREOISOMER PHARMACOKINETICS FOLLOWING IV ADMINISTRATION OF RS KETOROLAC TO CHILDREN. • 432

Ketorolac (KT) is administered as a racemic mixture although cyclooxygenase inhibitory activity resides with the (-S) stereoisomer. Little is known about KT stereo-specific pharmacokinetics. We studied plasma pharmacokinetics of(+R) and (-S) KT in 8 children (median age 11.8 yrs) following a 0.6 mg/kg IV dose of racemic KT. Twelve timed plasma samples were collected over 720 minutes after the dose. (+R)-KT and (-S)-KT were measured by HPLC using a CHIRACEL OJ-R column. Kinetic values were estimated from non-linear iterative fit of the the plasma concentrations to a bi-exponential or tri-exponential equation with 10 minutes infusion function. Significant differences were observed between the two enantiomers: Cmax was higher, AUC greater, t1/2elim longer, and Cl less for (+R)-KT. There was no difference between the enatiomers in Vd or t1/2dist. Table