Could saliva stand for plasma in theophylline monitoring in asthmatic children? Still a controversial problem.
Theophylline determination in saliva was proposed several years ago as a convenient and non-invasive alternative to monitoring plasma in children and adults. Published data demonstrated that theophylline saliva concentration linearly correlates plasma concentration. However, the variability found in interindividual serum/saliva ratios and the wide scattering among the data points precluded the clinical use of saliva for theophylline monitoring. The purpose of this study was to compare different standardized methods for obtaining stimulated saliva intending to reduce the variability in plasma/saliva ratios and to determine the most reliable one. A group of 150 ambulatory chronic asthmatic 4.5 to 20.83 (10 +/- 3.7; M +/- SD) year-old patients receiving theophylline 6.85 +/- 1.88 mg/kg every 12 h as slow release preparations for 4 to 100 days was studied. One ml venous blood and salivary specimens were simultaneously collected 5.15 +/- 0.36 h after the morning maintenance dose. In a subgroup of 75 patients, saliva was collected using first a new device called salivette, immediately followed by the collection of an expectorated sample 30 s after citric acid crystals stimulation. In the other patients saliva was collected using citric acid containing salivette. Theophylline concentration was determined using HPLC. For all types of saliva collection, salivary and plasma theophylline concentrations correlated significantly. However whichever method was used, based on the -2 to +2 SD interval, a large range of plasma theophylline was predicted from a single salivary theophylline concentration. Despite a further standardization of the sampling of saliva, saliva theophylline could not accurately predict plasma concentration.
Gao
Y
Y
Département de Pharmacologie Périnatale et Pédiatrique, Hôpital St-Vincent de Paul, Paris, France.
Pons
G
G
Rey
E
E
Richard
M O
MO
d'Athis
P
P
Bertin
L
L
Thiroux
G
G
de Blic
J
J
Scheinmann
P
P
Olive
G
G
D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D002648:Child; D003692:Delayed-Action Preparations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D012463:Saliva / Q000737:chemistry*; D013806:Theophylline / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood
D003692:Delayed-Action Preparations; D013806:Theophylline