Salivary theophylline monitoring: reassessment and clinical considerations.
To assess the reliability of salivary theophylline concentrations for patient monitoring, concentrations of theophylline in sera and saliva of 50 patients (ages 6-81 years) receiving oral or parenteral theophylline were determined by two methods: a rapid dry-phase apoenzyme reactivation system (ARIS) and fluorescence polarization immunoassay (FPIA). Saliva production was stimulated by both citric acid (CA) and parafilm (PF). With both analytical methods, there were excellent correlations between salivary theophylline concentration, CS, and unbound serum theophylline concentration CU (r2 > 0.95), and between CS and total serum theophylline concentration, CT (r2 > 0.85). CA- and PF-stimulated CS by FPIA resulted in concentrations within 2.0 micrograms/ml of the actual CU for 100% of the samples measured (n = 47). By ARIS, 100% of the PF-stimulated CS and 93.6% of the CA-stimulated CS determinations were within 2.0 micrograms/ml of the CU (n = 47). To evaluate the predictive capabilities of PF- and CA-stimulated saliva, one-half (n = 24) of the patients were randomly selected and their data used to predict the CT for the remaining patients. FPIA PF-CS predicted 83.3% (20/24) of CT within +/- 2 micrograms/ml, while ARIS CA-CS predicted 75.0% within +/- 2 micrograms/ml. There was no difference between FPIA CS and ARIS CS results by multivariate analysis of variance (MANOVA), but there was a difference between PF-CS and CA-CS (p < 0.05). However, when CU was used as a covariant, there was no significant difference. Using appropriate saliva collection procedures and the FPIA system, we conclude that CS provides adequate reliability for therapeutic drug monitoring of theophylline.
Kirk
J K
JK
Division of Pharmacy Practice, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
Dupuis
R E
RE
Miles
M V
MV
Gaddy
G D
GD
Miranda-Massari
J R
JR
Williams
D M
DM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001051:Apoenzymes / Q000032:analysis; D002648:Child; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010232:Paraffin / Q000494:pharmacology; D012463:Saliva / Q000737:chemistry*; D012472:Salivation / Q000187:drug effects; D013806:Theophylline / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics
D001051:Apoenzymes; D002951:Citrates; D019343:Citric Acid; D010232:Paraffin; D013806:Theophylline