603 STEADY STATE THEDPHYLLINE (T) PHARMACOKINETIC STUDIES (PK) IN CHILDREN. F. Chmelik, M.D., I. Jarmoszuk, M.D., M. Brown, M V 1 g p d', M.D., E. Miller, M.D., and H.J.*ZeTti,aMuD! Chicago, IL and Rockford, IL

36 asthmatic children, age 6-12, were enrolled in an open label randomized parallel group study to determine steady state T PK. After successful completion of a medical history, physical exam and baseline lab tests, 34 children were randomized to receive either a bead form of Theo-24, TheoBeads (TB) q12h (16 pts) or Theodur Sprinkle (TS) q8h (18 pts). They received T as outpatients for 6-22 days to achieve peak and trough serum T levels (STL) between lo-20 mcg/ml. They then were admitted to an inpatient clinical research unit (CRU) for serial STL q2h for 24h.

11 TB and 12 TS pt completed the study. Mean 24h T dosage in mg/kg (TB=19.4; TS=20.9) was virtually identical. Mean peak/trough STL, both prior to and during CRU admission were 15.6/12;6 and 17.1/8.5, respectively, for TB, and 14.3/13.0 and 18.3/9.5, respec- tively for TS. During PK, the STL % fluc- tuation (TB=101.8%; TS=93.6%) and % STL out of range (TB=31.4%; TS=26.8%) were not significantly different.

We conclude that in asthmatic children age 6-12, TB given q12h and TS given q8h maintain similar STL.

TIMING OF MAXIMUM AND MINIJMUM THEOPHYLLINE CONCENTRATION IN CHILDREN ON ONCE A DAY THEOPHYLLINE. Anthony R. Rooklin. M.D., Margaret J. Wolfgang, R.N., Sandra M.Gawchik, D.O., Chester, Pennsylvania.

The purpose of this study was to determine v&n maximum concentration (C-max) and minimum concentration (C-min) of theophylline (thee) would occur in children taking Theo-24 (T-24) once a day as a sprinkle.

Six healthy ambulatory children with asthma age 7-12 years (mean 9.0) were switched from bid dosing with Theodur to once a day dosing with T-24, using the same 24 hour total dose, given at 8 am. After 5 days on T-24 theo levels were drawn 8 and 24 hours post dose. Adjustments in dosage were made until the theo levels at both 8 and 24 hours fell between 8 and 20 mg/l. Two children required an adjustment in their dosage. Patients then took their 8 am dose after a 12 hour fast and 30 minutes before a low fat breakfast. Theo levels were drawn at 8 am and every 2 hours thereafter for 24 hours.

Three children had their C-max at 8 hours (mean 15.3) and 3 at 10 hours (mean 15.3).Three children had their C-min at 22 hours (mean 5.1) and 3 at 24 hours (mean 5.8). Results show that all 6 children had their C-max 8-10 hours post dose , C-min occurred in the last 2 hours of the 24 hour period. None of the children experienced either breakthrough wheezing or signs of toxicity.

For all 6 children C-max and C-min fell con- sistently at set times during the 24 hour dosing cyle. One could therefore predict the best time to evaluate C-max or C-min,making the transition from bid to once a day theo easier and safer.

605 COMPARISON OF TID SUSTAINED RELEASE THEOPHYLLINE WITH UNIPHYL, BID, IN SYMPTOM CONTROL OF CHILDREN WITH ASTHMA. S.M.Gawchik,DO;E.George,BS; W.A.Spiegel,MD; A.R.Rooklin,MD.,Chester,Pa.

Twenty children with well controlled chronic asthma 7-12 yrs of age (mean 9.2) on tid sustained release theophylline (SRT)were enrolled in an open ended study to evaluate the clinical efficacy of bid Uniphyl (U).

'.'he study was divided into Phase I and Phase II, each consisting of 7-14 days. During Phase I patients took SRT tid, kept symptom score cards (SSC)for chest tightness, cough, wheeze and difficulty breathing and did a peak flow (PF) at 8 am and 8 pm daily. During Phase II patients received bid U in the same total 24 hr dose as tid SRT. SSC and peak flows were done daily. On last day of both Phase I and II symptom scores were evaluated by an investigator, 8am serum theo level, FEVI and PF were done.

No statistically significant difference was noted between theophylline dose,theophylline Levels, P.F. FEVI and SSC. Variables (2 SRT I! P-Val :.?!:eo dose (me) 670 645 N.S. 2.Theo (mg/kg/day) 20.7 19.9 N.S. 3.PEFR (l/m) 225 239 N.S. 4.FEVI (1) 1.65 1.72 N.S. 5.Theo levels (mg/l) 13.0 12.2 N.S.

In conclusion, Uniphyl bid is as effective in controlling asthma as tid SRT. In addition an enhanced patient compliance can be expected as 17 out of 20 patients chose to remain on Uniphyl bid.

606

(S-R) TABLRTS IN CNIIQNRN WITR ASTIM. W.T.A. Watson. M.D., K.J. SM. Ph.D.. and P.B.R. simons. M.D., Winnipeg, Wanitoba, Canada.

E (3-propylxauthine), a new uethylxanthine bronchodilator, was studied in 10 asthmatic children, mean age 7.9 years. Serum E concen- trations (SEC) were measured before a dose of B 1 me/u I.V., then at 0.3, 0.6, 1.0, 1.5, 2.0, 2.5, 3, 4, 5, 6, and 8 hours (h). Vital signs end peak expiratory flow rate (PBPR) were monitored and urine was collected for 12 h. SEC and urine EC were measured by RPLC. The child- ren then ingested B S-R tablets, titrated up to 200 mg bid (7.5+1.3 mg/kg bid) for 8 days. On Day 9, pbarmacocinetic studies were repeated with frequent measurement of SEC over 12 h post-dose, and anotber 12-h urine collection.

The mean E serum elimination half-life was l.OS+SD 0.20 h, the clearance rate was 0.44+0.06 L/h/kg, and the steady-state volume of dzstribution wss 0.5520.05 L/kg. In the 12 h after the IV dose, 8728% unchanged E was recovered in the urine. On Day 9, the steady- state SEC was 1.720.5 mg/L. There was little fluctuation in SEC over 12 h; the peak/trough ratio was 3.0221.31. In tbe 12-h urine collection, so+l6% of unchanged B was recov- ered. Astbmasymptcm andPEERs remainedstable throughout the study. Vital signs were normal. Two patients had naueea after the I.V. dose.

We conclude that B has a short half-life in children, and is excreted largely unchanged in the urine. The E S-R tablets provide stable SEC and satisfactory relief of estbma throughout a 12-h dosing interval.

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