Para-aminosalicylic-acid (PAS) concentrations in the serum during treatment with various PAS preparations

Citron, K. M.; Kuper, S. W. A.

doi:10.1016/s0041-3879(59)80099-4

Cited by 9 publications

(11 citation statements)

References 7 publications

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“…The search terms used in various combinations were: "Aminosalicylic Acid"[MeSH], "para-aminosalicylic acid", "PAS", "efficacy", "intolerance", "dosage", "dose", "intravenous", "PK", "PD", "PK PD", "Pharmacokinetic*", "Pharmacokinetics compared to PAS salts. 22,[37][38][39] Similarly, the PASER formulation of PAS was designed to be better tolerated than earlier formulations and does appear to cause less gastrointestinal intolerance. [20][21][22][23]40,41…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the considerable interindividual and interoccasion variability found with different PAS formulations contributes to the challenges of using PAS. 21,23,37,[43][44][45] PAS can be a subject of drug interactions at both PK and PD levels. PAS absorption could be interfered with by antacid such as aluminium hydroxide because of its adsorption effect, 58 a later study, however, showed negligible effect on overall PAS exposure when PASER formulation was administered with a combination of aluminium hydroxide and magnesium hydroxide/simethicone.…”

Section: Pas Pkmentioning

confidence: 99%

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The pharmacokinetics of para‐aminosalicylic acid and its relationship to efficacy and intolerance

Abulfathi

Donald

Adams

et al. 2020

Brit J Clinical Pharma

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Following its introduction as an antituberculosis agent close to 75 years ago, the use of para‐aminosalicylic acid (PAS) has been limited by gastrointestinal intolerance and multiple formulations were produced in attempts to reduce its occurrence. More recently, an enteric‐coated, granular, slow‐release PAS formulation (PASER) was introduced and is now in wide‐spread use for the treatment of drug‐resistant tuberculosis. The current PASER dosing regimen is based on recommendations derived from older studies using a variety of different PAS formulations and relegate PAS to a role as an exclusively bacteriostatic agent. However, there is ample evidence that if sufficiently high serum concentrations are reached, PAS can be bactericidal and that intolerance following once daily dosing, that aids the achievement of such concentrations, is no worse than that following intermittent daily dosing. In particular, prevention of resistance to companion drugs appears to be dependent on the size of the single dose, and hence the peak concentrations, and not on maintaining serum levels consistently above minimum inhibitory concentration. We present a narrative review of the development of PAS formulations, dosing practices, and published data regarding pharmacokinetics and pharmacodynamics and the relationship of PAS dosage to intolerance and efficacy. Our conclusions suggests that we are at present not using PAS to its maximum ability to contribute to regimen efficacy and protect companion drugs.

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Section: Methodsmentioning

confidence: 99%

Section: Pas Pkmentioning

confidence: 99%

The pharmacokinetics of para‐aminosalicylic acid and its relationship to efficacy and intolerance

Abulfathi

Donald

Adams

et al. 2020

Brit J Clinical Pharma

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“…This difference is likely due to the slow absorption of the GR‐PAS formulation, which is designed to allow a prolonged period of PAS concentrations above the PAS minimum inhibitory concentration of 2 µg/mL . In this context, it should be recalled that a dose of 5‐g sodium PAS, such as that used during the well‐known British Medical Research Council studies that confirmed the efficacy of PAS in preventing resistance in companion drugs, led to mean C max concentrations of approximately 100 µg/mL …”

Section: Discussionmentioning

confidence: 99%

“…The absorption and metabolism characteristics of the various PAS formulations were affected. A number of studies showed that enteric coated PAS produced significantly lower serum concentrations compared to preparations of sodium PAS. Peloquin et al observed similar findings with administration of delayed‐release PAS.…”

mentioning

confidence: 99%

Pharmacokinetics of Para‐Aminosalicylic Acid and Its 2 Major Metabolites: A Potential Relationship to the Development of Gastrointestinal Intolerance

Adams

Donald

Abulfathi

et al. 2019

The Journal of Clinical Pharma

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Para‐aminosalicylic acid (PAS), often the last drug remaining for treatment of drug‐resistant tuberculosis, is notorious for causing gastrointestinal intolerance; however, the cause of PAS intolerance is uncertain. The objective of this study was to assess relationships between peak concentrations of PAS administered as a granular slow‐release enteric coated formulation, and its metabolites acetyl‐PAS and glycine‐PAS, and intolerance. PAS and its metabolites were measured in 29 adult patients with drug‐resistant tuberculosis at Brooklyn Hospital, Cape Town, randomized to receive granular slow‐release enteric‐coated PAS 4 g twice daily or 8 g once daily for 1 week, followed by the alternative regimen. Concentrations of PAS and its metabolites were determined by liquid chromatography and tandem mass spectrometry, and a visual analogue scale evaluated intolerance. Spearman's correlation test assessed the relationship between maximum plasma concentrations (Cmax) and intolerance scores. A large interindividual variability was observed for the PAS Cmax (40.42‐68.55 mg/L) following 4 g twice daily; (62.69‐102.41 mg/L) for 8 g once daily and a similar wide Cmax range found for the metabolites acetyl‐PAS and glycine‐PAS. Twenty‐six patients reported at least 1 intolerance episode, but most visual analogue scale scores clustered around 0. Significant inverse associations were found between acetyl‐PAS Cmax and bloating (rho = –0.448; P = .025) and diarrhea (rho = –0.407; P = .044) for the twice‐daily regimen and a similar inverse association found for glycine‐PAS and diarrhea (rho = –0.412; P = .041). Plasma concentrations of the metabolites did not correlate with the occurrence of gastrointestinal symptoms, but higher metabolite concentrations correlated with lower intolerance scores; slow metabolism of PAS and its continued presence in the intestinal tract may be the main cause of intolerance.

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“…should not be employed, and (b) even cachets containing isoniazid and sodium P.A.S. in accepted proportions cannot be relied upon to prevent drug resistance, have been strengthened respectively bv Citron and Kuper (1959) and Simpson (1959). A further simple urine test for P.A.S., using "phenistix " (Ames Co., Inc.), has also been investigated by Luntz (1959): we can fully confirm its efficacy and greater simplicity.…”

mentioning

confidence: 99%

Chemotherapeutic Pitfalls in the Treatment of Tuberculosis

Poole¹,

Stradling²

1960

BMJ

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Para-aminosalicylic-acid (PAS) concentrations in the serum during treatment with various PAS preparations

Cited by 9 publications

References 7 publications

The pharmacokinetics of para‐aminosalicylic acid and its relationship to efficacy and intolerance

The pharmacokinetics of para‐aminosalicylic acid and its relationship to efficacy and intolerance

Pharmacokinetics of Para‐Aminosalicylic Acid and Its 2 Major Metabolites: A Potential Relationship to the Development of Gastrointestinal Intolerance

Chemotherapeutic Pitfalls in the Treatment of Tuberculosis

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