Relationship between saliva salicylate concentration and free or total salicylate concentration in serum of children with juvenile rheumatoid arthritis

Levy, Gerhard; Procknal, Josephine A.; Olufs, Richard; Pachman, Lauren M.

doi:10.1038/clpt.1980.88

Cited by 16 publications

(7 citation statements)

References 10 publications

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“…Based on the good correlation between saliva con centrations in saliva and plasma in small number of subjects, several reports suggested that determination of salicylate in saliva may be useful in the monitoring of salicylate thera py [140-143]. A more extensive study in chil dren with juvenile rheumatoid arthritis con firmed the correlation between saliva and both free and total serum salicylate concentra tions, but a considerable intrasubject variabil ity in the saliva/serum salicylate concentra tion ratio was found [64],…”

Section: Salicylatementioning

confidence: 99%

Salivary Excretion of Drugs in Children: Theoretical and Practical Issues in Therapeutic Drug Monitoring

Gorodischer

Koren²

1992

Dev Pharmacol Ther

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Studies suggest that saliva could be used instead of blood in the therapeutic monitoring of many drugs. This has distinct advantages in pediatrics and neonatology as saliva sampling is painless and spares blood. Stimulation of saliva secretion with a chemical stimulus (i.e. citric acid applied over the tongue) facilitates the study of younger patients. Secretory and reabsorptive processes which take place in the ductal system of the salivary glands, and the rate of flow of the secretion play major roles in the determination of the concentration of solutes in saliva. Drug passage into saliva follows the general principles of movement of drugs across biologic membranes. Only the unbound fraction of the drug in plasma is available for diffusion into saliva and a relationship exists between saliva pH and the saliva/plasma concentration ratio of many polar drugs (tolbutamide, propranolol, procainamide, etc.). However, deviations from the pH theory exist and the inter- and intraindividual variations in saliva/plasma concentration ratios of salicylate and procainamide cannot be explained solely on the basis of fluctuations of salivary pH; on the other hand, a useful relationship exists between plasma and saliva phenobarbital concentrations with no need to correct for saliva pH. The use of stimulated saliva has several advantages over resting saliva: a larger volume of the sample is obtained, the pH gradient between plasma and saliva is smaller, the variability in saliva/plasma concentration ratios of some drugs is narrowed, and less specimens are too viscous or discolored to allow drug analysis. Thorough rinsing of the mouth is required prior to saliva sampling as remnants of orally administered medicines may contaminate saliva specimens and give spuriously high values. Deviation from a simple but strict methodology accounts for some of the discrepancies found in the literature. Studies in children uniformly recommend saliva for therapeutic monitoring of phenytoin, carbamazepine and phenobarbital. Saliva sampling for theurapeutic monitoring of ethosuximide, primidone and digoxin in infants and children, and of theophylline and caffeine in the neonate is promising, but little pediatric experience is available as yet. The value of saliva in therapeutic monitoring of theophylline in children is still controversial. Little of highly polar compounds such as aminoglycosides, and of polar highly protein bound drugs such as valproic acid is present in saliva. More data are still needed on the excretion of drugs in saliva in infants and in acutely ill children, and few data exist in the premature and full-term neonate.

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Section: Salicylatementioning

confidence: 99%

Salivary Excretion of Drugs in Children: Theoretical and Practical Issues in Therapeutic Drug Monitoring

Gorodischer

Koren²

1992

Dev Pharmacol Ther

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“…The utility of salivary salicylate determinations as a convenient and non-invasive indirect means of monitoring free salicylate concentrations in serum has recently been explored in a group of children with juvenile rheumatoid arthritis (Levy et al, 1980 DR BRUNE said that in the autoradiographic study reported he used a tritium label in the acetyl moiety, and in this particular situation there was a visible degree of labelling detected in the bone marrow compartment. He pointed out that aspirin acetylates cyclo-oxygenase, and speculated that it would occur in megakaryocytes, although there was at present no proof.…”

Section: Implications For Pharmacokinetic Monitoringmentioning

confidence: 99%

“…There is evidence from animal studies that this concept applies to salicylic acid (Reynolds & Cluff, 1960). As plasma protein binding of salicylate is concentration dependent, variable between individuals and affected by disease (evidence reviewed by Levy, Procknal, Olufs & Pachman, 1980), it is preferable in principle to monitor free rather than total salicylate concentrations in plasma or serum. However, determination of free drug in these fluids is time-consuming and costly, and therefore not suitable for routine clinical use with presently available methods.…”

Section: Implications For Pharmacokinetic Monitoringmentioning

confidence: 99%

Clinical pharmacokinetics of salicylates: a re‐assessment.

Levy¹

1980

Brit J Clinical Pharma

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1 Aspirin is partly hydrolyzed to salicylic acid during absorption. Absorbed aspirin is rapidly hydrolyzed systemically. Salicylic acid elimination kinetics are dependent on drug concentration due to the limited capacity of two major biotransformation pathways: formation of salicyluric acid and of salicylphenolic glucuronide. drug. As the plasma protein binding of salicylic acid is concentration-dependent and subject to pronounced interindividual differences, it is preferable, at least in principle, to monitor free rather than total concentrations of salicylate in plasma. Although salicylate concentration in saliva reflects the free rather than total salicylate concentration in plasma or serum, use of saliva for indirect monitoring of plasma salicylate concentrations seems to be impractical for technical reasons.

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“…Pharmacokinet. 21 (2) 1991 variation (coefficient of variation = 24%) in the ratio of mean saliva to serum salicylate concentrations (range of ratios 0.36 to 0.86) [Levy et al 1980). This is attributable, in part, to variation in salivary pH, to which salicylate concentrations are sensitive.…”

Section: Salicylalesmentioning

confidence: 98%

Clinical Pharmacokinetics of Drugs Used in Juvenile Arthritis

Skeith

Jamali

1991

Clinical Pharmacokinetics

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Juvenile arthritis is defined as the occurrence of objective evidence of arthritis for a minimum of 6 weeks, in a child 16 years of age or younger. With a reported incidence of 9 to 19.6 per 100,000 children, juvenile arthritis is considered to be a rare disease. There is no known cure; however, up to 75% of patients will undergo remission by late adolescence. Drugs used in the treatment of juvenile arthritis are divided into 2 major classes: (a) the nonsteroidal anti-inflammatory drugs (NSAIDs) including salicylates, naproxen, ibuprofen, fenoprofen, ketoprofen, flurbiprofen, indomethacin, sulindac, tolmetin and diclofenac, and (b) disease modifying agents which encompass drugs such as antimalarial agents, gold, methotrexate, penicillamine and sulfasalazine. In almost all the reports dealing with the pharmacokinetics of NSAIDs, the level of disease activity has not been noted. The level of activity is important since, during a flare, the plasma albumin may fall to the point that it causes a substantial and clinically significant increase in the unbound serum concentration of highly bound drugs. The relationship between the concentration of these drugs in the systemic circulation and their efficacy is not clear. However, for many of them, therapeutic drug monitoring is recommended as a means of reducing the possibility of toxic reactions. Further pharmacokinetic and -dynamic evaluations are needed for many of these drugs in juvenile arthritis.

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Relationship between saliva salicylate concentration and free or total salicylate concentration in serum of children with juvenile rheumatoid arthritis

Cited by 16 publications

References 10 publications

Salivary Excretion of Drugs in Children: Theoretical and Practical Issues in Therapeutic Drug Monitoring

Salivary Excretion of Drugs in Children: Theoretical and Practical Issues in Therapeutic Drug Monitoring

Clinical pharmacokinetics of salicylates: a re‐assessment.

Clinical Pharmacokinetics of Drugs Used in Juvenile Arthritis

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