Variations of serum concentrations and half‐life of salicylate in patients with rheumatoid arthritis

Paulus, Harold E.; Siegel, Mark; Mongan, Edward S.; Okun, Ronald; Calabro, John J.

doi:10.1002/art.1780140412

Cited by 93 publications

(31 citation statements)

References 7 publications

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“…were not obviously related to variations in their ability to produce and excrete salicyluric acid and salicyl phenolic glucuronide for the percentages of the total metabolites excreted as salicyluric acid and salicyl phenolic glucuronide by these two subjects were virtually identical ( Table 2) (Figure 2). When the daily dose of soluble aspirin was increased to 100 mg/kg for 3 days, in four patients, the plasma salicylate levels rose to a mean value of 34.5 mg/I00 ml (range 29.5-The wide variation of plasma salicylate levels reported in nine subjects by Paulus et al (1971) was not seen in this study, even though the dose of aspirin was identical (65 mg/kg body weight daily). This discrepancy might be partly due to the effect of albumin binding on plasma salicylate since those patients with the lower plasma values in the study of Paulus et al (1971) also tended to have lower serum albumin levels and one was frankly hypo-albuminaemic.…”

Section: Resultscontrasting

confidence: 57%

“…When the daily dose of soluble aspirin was increased to 100 mg/kg for 3 days, in four patients, the plasma salicylate levels rose to a mean value of 34.5 mg/I00 ml (range 29.5-The wide variation of plasma salicylate levels reported in nine subjects by Paulus et al (1971) was not seen in this study, even though the dose of aspirin was identical (65 mg/kg body weight daily). This discrepancy might be partly due to the effect of albumin binding on plasma salicylate since those patients with the lower plasma values in the study of Paulus et al (1971) also tended to have lower serum albumin levels and one was frankly hypo-albuminaemic. The low plasma salicylate levels of patients with rheumatoid arthritis reported by Bayles (1963) might also be explained on the basis of low serum albumin (Fremont Smith, 1963).…”

Section: Resultscontrasting

confidence: 57%

“…There may also be individual variations in the capacity for producing and excreting the major metabolite, salicyluric acid (Paulus, Siegel, Mongan, Okun & Calabro, 1971 pathway for excretion (Schachter & Manis, 1958). Both salicyluric acid and salicyl phenolic glucuronide are said to be rate limited in their formation and excretion (Levy & Tsuchiya, 1972).…”

Section: Introductionmentioning

confidence: 99%

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Kinetics of salicylate metabolism.

Gibson¹,

Zaphiropoulos²,

Grove³

et al. 1975

Brit J Clinical Pharma

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1Nine patients with rheumatoid arthritis or non-inflammatory backache were given soluble aspirin (65 mg/kg body weight) daily. There was no significant difference between the plasma salicylate of those with rheumatoid arthritis and those with backache. 2 Two patients had plasma salicylate values that differed significantly from the remainder but neither these results nor the marginal differences between plasma salicylate levels of the others could be explained by individual variations in the capacity for excreting salicyluric acid or salicyl phenolic glucuronide. 3 Increasing the dose of aspirin in four patients demonstrated the reduced proportions of salicyluric acid and salicyl phenolic glucuronide excreted at high doses and the increased importance of unchanged salicylic acid as an excretory pathway. These findings are consistent with a limiting capacity for salicyluric acid and salicyl phenolic glucuronide synthesis and excretion. 4 The findings in one patient suggested that inter-subject variations in the capacity for producing salicyl phenolic glucuronide and salicyluric acid may have an effect on plasma salicylate levels at high doses of aspirin.

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Section: Resultscontrasting

confidence: 57%

Section: Resultscontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Kinetics of salicylate metabolism.

Gibson¹,

Zaphiropoulos²,

Grove³

et al. 1975

Brit J Clinical Pharma

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“…Published reports demonstrate significant individual differences in salicylate elimination rates as well as serum salicylate levels at constant doses (3)(4)(5)(6)(7). However, no satisfactory explanation of this individual variability is documented.…”

Section: Introductionmentioning

confidence: 99%

Salicylate Metabolism in Twins

Fürst¹,

Gupta²,

Paulus³

1977

J. Clin. Invest.

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A B S T R A C T To evaluate the contribution of genetic influences on the individual variation in plateau serum salicylate levels, salicylate metabolism was studied in seven pairs of identical and six pairs of fraternal twins.Under the conditions of this study, after a single i.v. dose (40 mg/kg) of sodium salicylate, the serum salicylate concentration versus time curve approximated a straight line on linear coordinates (appeared approximately zero order). The slopes of the decay curves ranged between 0.64 and 1.02. The intrapair variation for identical twin pairs was significantly less than for fraternal twin pairs (P = 0.044). Likewise pleateau serum salicylic acid concentrations (milligrams/deciliter) and total salicylic acid excretion rate after multiple doses demonstrated significantly less intrapair variation for identical twins than for fraternal twins (P = 0.043 and 0.006). Plateau salicylurate excretion (milligram/kilogram per hour) differences after multiple dosing had a P = 0.067. Michaelis-Menton constant for salicylurate formation and hours to 50% excretion after the i.v. dose were not different when comparing identical and nonidentical twins.Salicylurate formation rates were increased after 3 days of oral therapy, and this induction phenomenon may account for much of the apparent discrepancy between genetic influences on salicylurate formation rates observed after single and multiple dose salicylate administration.This study suggests that the plateau concentration of serum salicylate varies among individuals given the same weight-adjusted dose in part because of genetiDr. Furst's present address is the

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“…In contrast, salicylate accumulation occurs in man during continuous therapy. When aspirin is given every 8 hours, plateau drug concerltrations are reached after 6 to 9 doses of 500 mg each or after 20 doses of 1000 mg each (27,28). Thus it is likely that high blood levels are better maintained in humans than in mice.…”

Section: Discussionmentioning

confidence: 99%

Effect of sodium salicylate on human and mouse granulopoiesis in vitro

Gabourel

Moore

Bagby

et al. 1977

Arthritis & Rheumatism

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Sodium salicylate inhibited generation of granulocyte and macrophage colonies when added to soft agar cultures of mouse or human bone marrow cells (CFUc) containing colony-stimulating factor (CSF). This effect was dose-dependent with over 90% inhibition at 48 mg%. The salicylate effect was not decreased with increasing concentrations of CSF, but inhibition was reversed when salicylate-treated CFUc were washed with drug-free medium before plating. CSF production was not inhibited by salicylate.Recently a number of drugs, phenobarbital (I), diphenylhydantoin (2), halothane and other anesthetics (3-5), salicylates (6-8), and oral contraceptives (9) have

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Variations of serum concentrations and half‐life of salicylate in patients with rheumatoid arthritis

Cited by 93 publications

References 7 publications

Kinetics of salicylate metabolism.

Kinetics of salicylate metabolism.

Salicylate Metabolism in Twins

Effect of sodium salicylate on human and mouse granulopoiesis in vitro

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