Reliability of Salivary Theophylline as a Guide to Plasma Theophylline Levels

Abstract

\s=b\Simultaneous saliva and plasma theophylline levels in 12 chronic asthmatic children were measured by high pressure liquid chromatography following administration of a theophylline preparation. In five subjects, simultaneous plasma and salivary theophylline were measured one week later. A strongly positive correlation between plasma and salivary theophylline levels was found at all time periods tested.There was no substantial difference in the plasma-saliva theophylline ratio determined one week later. A predicted plasma Recent studies on drug therapy of ' patients with bronchial asthma have suggested the use of higher doses of theophylline than those previously recommended.1 In using such high doses, it is desirable to monitor the plasma concentration to indicate whether either therapeutic or potentially toxic levels have been reached.2 Pharmacokinetic studies in asthmatic patients show considerable variability in the plasma half-life of theophylline,3 with a range of 1.42 to 7.85 hours in children.4 Therefore, an appropriate dosage program for one patient may not be suitable for another. Determination of plasma levels at various time periods followFrom the Department of Pediatrics, University of California at Irvine. Reprints are not available.level was compared with the observed value. The proportionality of predicted to observed plasma theophylline levels using either the entire study group mean plasma-saliva ratio or each individual's ratio was approximately 1.00 with 9% variability. When a previously reported plasma-saliva theophylline ratio was used for comparison, the predicted plasma theophylline was 15% above the observed plasma level. (Am J Dis Child 131: [970][971][972] 1977) ing drug administration could estab¬ lish the high and low values and the rapidity of clearance (half-life) from the plasma. This would have great relevance in determining the proper dose. The obvious objection, particu¬ larly in the pediatrie age patient, is the discomfort and inconvenience of the multiple blood samples required. Koysooko et al5 found that a constant ratio existed between simul¬ taneously obtained plasma and saliva theophylline concentrations in normal adults. In a subsequent study involv¬ ing asthmatic children, these investi¬ gators were able to predict the plasma theophylline levels within 20% of the actual values by multiplying the mea¬ sured saliva theophylline level by the previously established plasma/saliva ratio." However, one recent report failed to confirm the consistency of this ratio.7 In the present study, we report the hourly variability of the plasma-saliva ratio, as well as the week-to-week consistency of the ratio, in the same patient. We also have compared the accuracy of predicting plasma theophylline levels using each individual's plasma-saliva ratio, the mean ratio of our entire group, and the mean ratio for the asthmatic patients reported in the literature." SUBJECTS AND METHODSTwelve asthmatic children (aged 6 to 14 years) were given 3.0 to 8.1 mg/kg of anhydrous theophylline every...

Theophylline Concentrations in Serum and Saliva after Oral Microcrystalline and Sustained‐Release Preparations in Asthmatics

“…At the same time, several investigators (6,9,11) have shown that saliva concentration measurement provides a reliable measure of serum concentration. At the same time, several investigators (6,9,11) have shown that saliva concentration measurement provides a reliable measure of serum concentration.…”

“…The appearance of sustained-release theophylline preparations has made it possible to obtain stable theophylline concentrations with 12 hourly dosing intervals (4, 10, 13, 15). At the same time, several investigators (6,9,11) have shown that saliva concentration measurement provides a reliable measure of serum concentration. If this is true then treatment with theophylline drugs would be made much easier.…”

Do saliva concentrations predict plasma unbound theophylline concentrations? A problem re‐examined.

“…S/P ratio of 0.568 0.008 and the same relationship between saliva and plasma was found in subjects of all ages ( Figure 1). Although other laboratories obtained similar ratios in children Eney & Goldstein, 1976;Galant et al, 1977;Kelly et al, 1981;Goldsworthy et al, 1981), Khanna and colleagues (1980) found the saliva theophylline concentrations approximated to 0.76-0.8 of plasma theophylline concentrations in neonates. Further studies are clearly needed to confirm the S/P ratio in neonates found in this study.…”

A prospective trial using salivary‐theophylline levels to guide asthma therapy

“…standard deviation; range, [4][5][6][7][8][9][10][11][12][13][14][15][16][17] were collected simulta-Theophylline is widely used in the treatment of chronic obstructive airway diseases in children. Because of the low therapeutic index of theophylline ' careful monitoring of serum-theophylline levels has been advocated.…”