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

Abstract

Theophylline concentrations in saliva have been compared with those in serum in 13 asthmatic patients after single and multiple oral dosage of a microcrystalline theophylline tablet (Nuelin) and a sustained-release preparation (Nuelin Retard). There was wide individual variation in the ratio of serum to saliva concentrations indicating that, even when individual serum to saliva ratios have been established, the use of saliva theophylline measurements alone is unreliable for the routine monitoring of theophylline therapy. Both preparations produced mean serum theophylline concentrations within the 10--20 mcg/ml range, the sustained-release tablet giving higher monitoring through values and smaller through to peak variation. The preparations were equally and highly bioavailable. Side effects were reported by three patients, which were the patients with the highest AUC. The Nuelin Retard preparation appears to provide smooth, sustained serum theophylline concentrations within the therapeutic range and the simple, twice-daily dosage should result in improved patient compliance.

Reproducibility of saliva and plasma theophylline levels following single dose administration of two sustained release preparations.

“…This study confirms the work of others (Boobis et al, 1979;Munch et al, 1981;Sharma et al, 1981) Saliva theophylline (pg ml1) Figure 2 The relationship between plasma and saliva theophylline levels for three subjects (A, B and C) each studied on three occasions. Correlation coefficients have been calculated where the relationship appeared linear.…”

Could saliva stand for plasma in theophylline monitoring in asthmatic children? Still a controversial problem

“…All previous published data demonstrated that theophylline saliva concentration correlates linearly plasma concentration Levy et al, 1974;Shah et (11, 1974;Johnson et al, 1975;Eney and Goldstein, 1976;Hendeles et al, 1977;Galant et al, 1977;Danhof et al, 1978;Boobis et al, 1979;Lena et al, 1980;Khanna et ul, 1980;Kelly et al, 1981;Goldsworthy et al, 1981;Jonkman et al 1981;Munch et (11, 1981;Sharma et al, 1981;Knott et al 1984;Gozal et (11, 1985;Ohmori et al, 1986;Boner et (11, 1986;Trnavska et al, 1987;Jaber et al, 1987;Orlowski et ul, 1987;Iwasaki and Baba, 1987;Aviram et rrl, 1987;Juntunen et al, 1988;Siege1 et al, 1990;Bidat et ul, 1990). However, the variability found in interindividual serudsaliva ratios and the wide scattering among the data points obtained with nonstimulated saliva actually precluded the clinical use of non-stimulated saliva measurements for the assessement of serum concentration of theophylline (Hendeles et al, 1977;Galant et ul, 1977;Danhof and Breimer, 1978;Boobis et ul, 1979;Jonkman et al, 1981;Kelly et ul, 1981;Munch et al 1981;Sharma et al, 1981;Boner et id, 1986;Iwasaki and Baba, 1987). This also holds true for teflon and paraffin stimulated saliva (Hendeles et a], 1977; Kelly et al, 1981; de Marino et al, 1986;Boner et al, 1985…”

Phyllocontin in Chronic Airflow Obstruction

“…The main factor limiting the use of theophyllines has been the high incidence of side effects 4 and in the past frequent dosage was necessary to maintain therapeutic levels. Controlled release formulations have been shown to give adequate serum levels with a twice daily dosage 5 . It is interesting to note that recent studies have shown no direct relationship between serum levels and side effects 6,7 and up to 15 per cent of patients seem unable to tolerate oral theophyllines, even in low dosage 8 …”