The consequences of H2 receptor antagonist ? piroxicam coadministration in patients with joint disorders

Milligan, Peter A.; McGill, P E; Howden, Colin W.; Kelman, Andrew W.; Whiting, B.

doi:10.1007/bf00315306

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…For dissolution studies, the samples were tested with the dispersed amounts method (17) by placing 10 mg of piroxicam or its equivalent in coprecipitates or in physical mixtures on the surface of the dissolution medium. Aliquots (5 mL) were withdrawn at 2, 4,6,8,10,15,20,30,40, and 60 min and replaced with 5 mL of fresh dissolution medium. The amounts of piroxicam in dissolution media pH 1.2 and pH 4.0 were determined using UV spectroscopy at 344 and 356 nm, respectively.…”

Section: Dissolution Studiesmentioning

confidence: 99%

“…According to some studies, the coadministration of cimetidine and piroxicam does not impair the efficacy of piroxicam or cause any adverse effects (8) but can increase the plasma concentrations of piroxicam (9). Recent studies have demonstrated that coprecipitation of cimetidine and piroxicam at a 1:1 mole ratio can transform the crystalline structures of both drugs to an amorphous state (manuscript in preparation).…”

Section: Introductionmentioning

confidence: 99%

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Crystal Structure Transformations and Dissolution Studies of Cimetidine–Piroxicam Coprecipitates and Physical Mixtures

et al. 2009

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Abstract. We have recently demonstrated that coprecipitation of cimetidine (C) and piroxicam (P) at a mole ratio of 1:1 results in the transformation of the crystalline forms of both drugs to an amorphous state. In this study, coprecipitates and physical mixtures of cimetidine and piroxicam were further investigated at C/P mole ratios of 1:10, 1:5, 1:4, 1:2, 10:1, 20:1, 30:1, 40:1, and 52.5:1, the latter being the composition of a clinically used dosage. The physicochemical properties of these samples were examined using X-ray diffraction and Fourier transform infrared spectroscopy. Additionally, dissolution of piroxicam in the samples at C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 was investigated at pH 1.2 and pH 4. In coprecipitates with C/P mole ratios of 10:1, 20:1, 30:1, and 40:1, crystalline forms of both drugs were transformed to amorphous states. A mixture of an amorphous state and cimetidine crystalline form A was observed for the coprecipitate with a C/P mole ratio of 52.5:1. For the coprecipitates with C/P mole ratios of 1:2, 1:4, 1:5, and 1:10, cimetidine form A was transformed to form C, whereas piroxicam form II was modified to form I. It is interesting that small molecules, instead of polymers or solvents, can cause such crystal structure transformations. The dissolution of piroxicam at pH 4 is lower than that at pH 1.2. Additionally, the coprecipitates and physical mixtures with C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 demonstrate substantially higher dissolution of piroxicam compared to that of drug alone.

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Section: Dissolution Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Crystal Structure Transformations and Dissolution Studies of Cimetidine–Piroxicam Coprecipitates and Physical Mixtures

et al. 2009

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“…In a small study in patients with joint disorders comparing the consequences of coadministration of the H2-receptor antagonists cimetidine and nizatidine with piroxicam, no clinically significant alteration in the steady-state pharmacokinetics of piroxicam occurred. [80] The AVC of salicylic acid is not altered by cimetidine or ranitidine.l 42 )…”

Section: Histamine H2-receptor Antagonistsmentioning

confidence: 98%

Pharmacokinetic-Pharmacodynamic Drug Interactions with Nonsteroidal Anti-Inflammatory Drugs

Brouwers¹,

Smet

1994

Clinical Pharmacokinetics

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The nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly prescribed, especially in the elderly population. In many countries more than 10 different NSAIDs are available. As the older pyrazole compounds like phenylbutazone, oxyphenbutazone and azapropazone are most prone to pharmacokinetic interactions, the use of these compounds should be avoided where possible. Acidic NSAIDs interact with bile acid-binding resins, resulting in decreased concentrations of NSAIDs in the blood. In earlier reports it was suggested that the absorption of NSAIDs was affected by antacids and sucralfate. More recently, it was shown that there is delayed absorption of these drugs, but there is no difference in the extent of absorption. Only salicylates had their urinary secretion enhanced by antacids, which increase the urinary pH to values > 7. Histamine H2-receptor antagonists can be combined safely with NSAIDs. The concomitant administration of probenecid increased the blood concentration of NSAIDs, so an enhanced anti-inflammatory effect can be expected when these 2 drugs are combined. More importantly, NSAIDs can cause pharmacokinetic drug-drug interactions with other drugs. As can be expected, interactions with drugs that have a small therapeutic window are most likely to be of clinical significance. For example, lithium, medium to high dose methotrexate and, to a lesser extent, cyclosporin may be affected by concomitant administration of an NSAID. Aspirin (acetylsalicylic acid) and/or pyrazoles interact with oral anticoagulants, oral antihyperglycaemic agents and the anticonvulsants phenytoin and valproic acid (sodium valproate). Elevation of blood concentrations of these agents can be potentially dangerous. Similarly, NSAIDs interact with digoxin. This interaction is most likely to occur in the elderly, in neonates or in patients with renal impairment. Indomethacin can influence the blood concentrations of aminoglycosides in neonates. Unfortunately, this effect seems unpredictable, so practical therapeutic recommendations cannot be made. When NSAIDs are combined with salicylates or diflunisal, the blood concentrations of the salicylate or diflunisal may increase. However, the clinical relevance of this increase in drug concentration seems to be of minor importance. Gastrointestinal bleeding caused by NSAIDs is the most dangerous when it results from a mixed pharmacokinetic/pharmacodynamic interaction; however, patients are also at risk when pharmacodynamic interactions only are involved.

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“…The concomitant administration of cimetidine and piroxicam does not result in any impairment of the efficacy of piroxicam, or cause any adverse effect (8), but co-administration of cimetidine can result in an increase in the plasma concentrations of piroxicam (9). The preparation of binary mixtures of some drugs has been reported to be accompanied by a change in the crystalline structures of the starting drugs (10,11).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Cimetidine–Piroxicam Coprecipitate Interaction Using Experimental Studies and Molecular Dynamic Simulations

2010

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Abstract. The crystalline states of cimetidine and piroxicam, when coprecipitated from solvents containing 1:1 mole ratio, were transformed to amorphous states as observed using powder X-ray diffraction (PXRD). Amorphous forms of drugs generally exhibit higher water solubility than crystalline forms. It is therefore interesting to investigate the interactions that cause the transformation of both the crystalline drugs. Intermolecular interactions between the drugs were determined using Fouriertransform infrared spectroscopy (FTIR) and solid-state 13 C CP/MAS NMR. Molecular dynamic (MD) simulation was performed for the first time for this type of study to indicate the specific groups involved in the interactions based on radial distribution function (RDF) analyses. RDF is a useful tool to describe the average density of atoms at a distance from a specified atom. FTIR spectra revealed a shift of the C≡N stretching band of cimetidine. The 13 C CP/MAS NMR spectra indicated downfield shifts of C 11 , C 15 and C 7 of piroxicam. RDF analyses indicated that intermolecular interactions occurred between the amide oxygen atom as well as the pyridyl nitrogen of piroxicam and H-N 3 of cimetidine. The hydrogen atom (O-H) at C 7 interacts with the N 1 of cimetidine. Since the MD simulation results are consistent with, and complementary to the experimental analyses, such simulations could provide a novel strategy for investigating specific interacting groups of drugs in coprecipitates, or in amorphous mixtures.

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The consequences of H2 receptor antagonist ? piroxicam coadministration in patients with joint disorders

Cited by 6 publications

References 25 publications

Crystal Structure Transformations and Dissolution Studies of Cimetidine–Piroxicam Coprecipitates and Physical Mixtures

Crystal Structure Transformations and Dissolution Studies of Cimetidine–Piroxicam Coprecipitates and Physical Mixtures

Pharmacokinetic-Pharmacodynamic Drug Interactions with Nonsteroidal Anti-Inflammatory Drugs

Characterization of Cimetidine–Piroxicam Coprecipitate Interaction Using Experimental Studies and Molecular Dynamic Simulations

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