Drug Interaction in Psoriasis

Adams, John; Hunter, G. A.

doi:10.1111/j.1440-0960.1976.tb00587.x

Cited by 30 publications

(9 citation statements)

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“…"=' 50%), displacement from protein by other drugs is unlikely to be of significant clinical importance. Drugs that have been reported to displace methotrexate from albumin include salicylates, probenecid, barbiturates, phenylbutazone, doxorubicin (adriamycin), and phenytoin (diphenylhydantoin) [Adams & Hunter 1976;Beach et al 1981;Coassolo et al 1980;Dixon et al 1965;Paxton 1984;Taylor & Halprin 1977]. The clinical significance of these interactions is not known; however, since salicylate and probenecid can also decrease renal tubular secretion of methotrexate (Bourke et al 1975;Liegler et al 1969), caution should be used when these drugs are given concomitantly.…”

Section: Distributionmentioning

confidence: 95%

Pharmacokinetics of Anticancer Drugs in Children

Crom

Glynn-Barnhart

Rodman

et al. 1987

Clinical Pharmacokinetics

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Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of distribution, hepatic (doxorubicin, cyclophosphamide), and renal (bleomycin, methotrexate) clearances. These differences in pharmacokinetics as a function of age alter systemic exposure to chemotherapy, and may alter the efficacy and toxicity profile for standard doses of antineoplastic drugs. The relationship of systemic exposure to toxicity has been most clearly defined for methotrexate. Clinical monitoring of methotrexate serum concentrations, and adjustment of folinic acid dosages and duration of rescue based on methotrexate disposition is now routine. More recently, pharmacodynamic data have been published for high-dose methotrexate, epipodophyllotoxins, cisplatin, and cytarabine (cytosine arabinoside), indicating a relation between drug disposition and toxicity or efficacy. Collectively, these data suggest that the pharmacokinetics of many anticancer drugs in children is different from adults, and that variability in drug disposition may have an important influence on toxicity or efficacy.

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Section: Distributionmentioning

confidence: 95%

Pharmacokinetics of Anticancer Drugs in Children

Crom

Glynn-Barnhart

Rodman

et al. 1987

Clinical Pharmacokinetics

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“…A high concentration of salicylate was required to inhibit the transport activity by rOat1, rOat3, and RFC-1. NSAIDs, such as diclofenac, indomethacin, ketoprofen, phenylbutazone, and naproxen, which have been reported to cause severe drugdrug interactions with MTX (Adams and Hunter, 1976;Ellison and Servi, 1985;Thyss et al, 1986;Ng et al, 1987), showed a potent inhibitory effect on rOat3 but had only a minimal effect on RFC-1.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Evaluation of the Drug-Drug Interactions between Methotrexate and Nonsteroidal Anti-Inflammatory Drugs in the Renal Uptake Process Based on the Contribution of Organic Anion Transporters and Reduced Folate Carrier

Nozaki

Kusuhara²,

Endou³

et al. 2004

J Pharmacol Exp Ther

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The present study examined the possible role of transporters in the drug-drug interactions between methotrexate (MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs) in the renal uptake process of MTX. MTX is recognized by reduced folate carrier (RFC-1) and rat organic anion transporters (rOat1 and rOat3) as a substrate. Uptake of MTX by kidney slices was saturable and inhibited potently by dibromosulfophthalein. Folate and benzylpenicillin (PCG) inhibited the uptake by 30 to 40% and 40 to 50% of the total saturable uptake of MTX by kidney slices, respectively, whereas the effect of p-aminohippurate (PAH) was minimal at the concentration selective for rOat1. In contrast, the uptake of 5-methyltetrahydrofolate by the kidney slices was inhibited by MTX, folate, and dibromosulfophthalein, but not by PAH and PCG. These results suggest that rOat3 and RFC-1 are almost equally involved in the uptake of MTX by the kidney slices, whereas RFC-1 is responsible for the renal uptake of 5-methyltetrahydrofolate. NSAIDs, except salicylate, were potent inhibitors of rOat3 (K i of 1.3-19 M), but weak inhibitors of RFC-1 (K i of 70 -310 M). This is in a good agreement with the biphasic inhibition profiles of NSAIDs for the uptake of MTX by kidney slices. These results suggest that the renal uptake of MTX is not so greatly affected by NSAIDs as expected from the inhibition of rOat3-mediated transport.Drug-drug interactions involving metabolism and/or excretion process prolong the plasma elimination half-lives, leading to the accumulation of drug in the body after repeated administration, and potentiate pharmacological/adverse effects. Investigating the mechanism of a drug-drug interaction is important as far as achieving safer chemotherapy is concerned. Transporters are one of the determinant factors governing drug disposition together with metabolic enzymes and have been regarded as important drug-drug interaction sites in the body (Ito et al., 1998). Recent progress in molecular biological research has shown that many types of transporters play important roles in the tissue uptake and/or subsequent secretion of drugs in the liver and kidney, and enables us to examine the incidence of drug-drug interactions involving membrane transport based on the contribution of the transporters to the membrane transport of the drugs in question.Methotrexate (MTX) is an analog of natural folate and has been used not only for the treatment of neoplastic diseases (Evans et al., 1986) but also autoimmune diseases including rheumatoid arthritis (Giannini et al., 1992) and psoriasis (Chladek et al., 1998). Numerous case reports have indicated that coadministration of MTX with penicillin, probenecid, and nonsteroidal anti-inflammatory drugs (NSAIDs) cause drug-drug interactions, which affect the pharmacokinetic parameters of MTX (Furst, 1995). To date, several potential sites have been proposed for these drug-drug interactions: an increase in the unbound fraction of MTX (Tracy et al., 1992), a decrease in the urine flow rate resulting from ...

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“…Reports indicate severe and sometimes lifethreatening interactions between methotrexate and some NSAIDs: salicylates (Mandel 1976), indomethacin (Maiche 1986), ketoprofen (Thyss et al 1986), phenylbutazone (Adams & Hunter 1976) and naproxen (Singh et al 1986). A pharmacokinetic explanation has been provided for the interaction with ketoprofen (Thyss et al 1986).…”

Section: Methotrexatementioning

confidence: 96%

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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Drug Interaction in Psoriasis

Cited by 30 publications

References 0 publications

Pharmacokinetics of Anticancer Drugs in Children

Pharmacokinetics of Anticancer Drugs in Children

Quantitative Evaluation of the Drug-Drug Interactions between Methotrexate and Nonsteroidal Anti-Inflammatory Drugs in the Renal Uptake Process Based on the Contribution of Organic Anion Transporters and Reduced Folate Carrier

Clinical Pharmacokinetics of Drugs Used in Juvenile Arthritis

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