Abstract
The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug.
Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0–4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0–4 h was significantly increased (5.6 μg · ml−1 · h vs 4.5 μg · ml−1 · h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0–4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65).
These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.
This is a preview of subscription content, log in via an institution to check access.
References
Bochner F, Hooper WD, Sutherland JM, et al (1974) Diphenylhydantoin concentrations in saliva. Arch Neurol 31: 57–59
Cook CE, Amerson E, Poole WE, et al (1976) Phenytoin and phenobarbital concentrations in saliva and plasma measured by radioimmunoassay. Clin Pharmacol Ther 18: 742–747
Paxton JW, Rowell FJ, Ratcliffe JG (1976) Production and characterization of antisera to diphenylhydantoin suitable for radioimmunoassay. J Immunol Methods 10: 317–327
Paxton JW, Whiting B, Stephen KW (1977) Phenytoin concentrations in mixed, parotid and submandibular saliva and serum measured by radioimmunoassay. Br J Clin Pharmacol 4: 185–191
Keen P (1960) Therapeutic drug monitoring in saliva. In: Brodie BB, Gillette JR and Ackerman HS (eds) Concepts in biochemical pharmacology, part 1. Springer, Berlin Heidelberg New York, pp 213–233
Reynolds F, Ziroyanis PN, Jones NF, et al (1976) Salivary phenytoin concentrations in epilepsy and in chronic renal failure. Lancet II: 384–386
Kamali F, Edwards C, Rawlins MD (1992) The effect of pirenzepine on gastric emptying and salivary flow rate: constraints on the use of saliva paracetamol concentrations for the determination of paracetamol pharmacokinetics. Br J Clin Pharmacol 33: 309–312
Dollery CT, Davies DS, Draffan GH, et al (1975) Clinical Pharmacology and pharmacokinetics of clonidine. Clin Pharmacol Ther 19: 11–17
Kabra PM, Nelson MA, Marton LJ (1983) Simultaneous very fast liquid-chromatographic analysis of ethosuximide, primidine, phenobarbital, phenytoin, and carbamazepine in serum. Clin Chem 29: 473–476
Leonard R (1980) Phenytoin binding in pregnancy. Lancet II: 1312–1313
Knott C, Reynolds F (1984) The place of saliva in antiepileptic drug monitoring. Ther Drug Monit 6: 35–41
Virtanen R, Kanto J, Iisalo E, Iisalo EUM, Salo M, Sjovall S (1982) Pharmacokinetic studies on atropine with special reference to age. Acta Anaesthesiol Scand 26: 297–300
Richens A (1979) Clinical Pharmacokinetics of phenytoin. Clin Pharmacokinet 4: 153–169
Perucca E, Ruprah M, Richens A (1981) Decreased serum protein binding of phenytoin in late pregnancy. Br J Clin Pharmacol 12: 276
Lunde PKM, Rane A, Yaffe SJ, Lund J, Sjoqvist F (1970) Plasma protein binding of diphenylhydantoin in man. Interaction with other drugs and the effect of temperature and plasma dilution. Clin Pharmacol Ther 11: 846–855
Reidenberg M, Odar-Cederlof I, Von Bahr C, Borga O, Sjoqvist F (1971) Protein binding of phenytoin and desmethylimipramine in plasma from patients with poor renal function. N Engl J Med 285: 264–265
Odar-Cederlof I, Borga O (1974) Kinetics of phenytoin in uremic patients: consequence of decreased plasma protein binding. Eur J Clin Pharmacol 17: 31–37
Patsalos PN, Lascelles PT (1977) Valproate may lower serum phenytoin. Lancet I: 50–51
Monks A, Boobis S, Wadsworth J, Richens A (1978) Plasma protein binding interaction between phenytoin and valproic acid in vitro. Br J Clin Pharmacol 6: 487–492
Friel PN, Leal KW, Wilensky AJ (1979) Valproic acid-phenytoin interaction. Ther Drug Monit 1: 243–248
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kamali, F., Thomas, S.H.L. Effect of saliva flow rate on saliva phenytoin concentrations: implications for therapeutic monitoring. Eur J Clin Pharmacol 46, 565–567 (1994). https://doi.org/10.1007/BF00196118
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00196118