Pharmacokinetics of diclofenac sodium after intramuscular administration in combination with triamcinolone acetate

Derendorf, Hartmut; Mullersman, Gotelind; Barth, Jürgen; Grüner, Alf

doi:10.1007/bf00981139

Cited by 14 publications

(9 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the three trials described in the present paper, t max with test formulations was reached remarkably faster, even with the film coated tablets (Trial 2), as shown in Table 4. These t max values are shorter even than peak times obtained by other authors [11,12] after intramuscular administration of diclofenac sodium salt. According to these authors, the diclofenac peak was in fact reached 15 [11] and 25 min [12] after dosing.…”

Section: Discussioncontrasting

confidence: 57%

Increased Absorption Rate of Diclofenac from Fast Acting Formulations Containing Its Potassium Salt

Reiner

et al. 2011

Arzneimittelforschung

View full text Add to dashboard Cite

Diclofenac (CAS 15307-86-5) is a non-steroidal anti-inflammatory drug largely used, mainly to relief pain of various origin. Diclofenac is present on the market as free acid, as sodium salt (CAS 15307-79-6) and as potassium salt (CAS 15307-81-0). The last salification form has shown a prompter absorption rate and a faster onset of analgesic activity than the acid form and sodium salt. This paper extensively reviews three trials carried out on healthy volunteers, where potassium salt of diclofenac present in three fast-acting formulations, namely sachets (Trial 1), tablets (Trial 2) and oral drops (Trial 3), were compared to reference tablet formulations from the market. A very fast absorption rate was encountered with the three test formulations, with the peak reached in one case 5 min and in most cases within 10-15 min after dosing. The quick absorption rate of test formulations was attributed to the special combination of the salt of diclofenac with a dynamic buffering agent, namely bicarbonate, present in the test formulations and covered by an international patent. The prompt absorption of diclofenac from the new fast-acting formulations was accompanied by the presence of only one peak, whereas the reference formulations produced in most cases two peaks, as widely described in literature. This finding suggested the hypothesis that the absorption of test formulations should occur in a shorter tract of the gut. The faster absorption of diclofenac from the three fast-acting formulations is expected to produce a faster onset of analgesic action, which highlights these new formulations as particularly indicated to relief pain of any origin.

show abstract

Section: Discussioncontrasting

confidence: 57%

Increased Absorption Rate of Diclofenac from Fast Acting Formulations Containing Its Potassium Salt

Reiner

et al. 2011

Arzneimittelforschung

View full text Add to dashboard Cite

show abstract

“…They speculated that the pharmacokinetic interaction, which is unique to diclofenac, was caused by the inhibition in the ®rst-pass metabolism of diclofenac by cyclosporin. On the other hand, Derendorf et al (1986) detected a slight increase (approximately 20%) in the C max of diclofenac after intramuscular administration of a combination of diclofenac and triamcinolone acetate. Figure 3 shows the mean ketoprofen plasma concentration±time pro®les after oral dosing of 1 mg kg À1 alone or when co-administered with AZT (1Á5 mg kg À1 , p.o.)…”

Section: Drugmentioning

confidence: 88%

Zidovudine, Diclofenac and Ketoprofen Pharmacokinetic Interactions in Rats

Radwan

2000

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Zidovudine (AZT) is widely used for the management of human immunodeficiency virus (HIV) infections. Non-steroidal anti-inflammatory drugs (NSAIDs) are often used for relief of non-specific fever and musculoskeletal pain in patients with HIV including those with AZT-induced myopathy. The effects of single oral doses of diclofenac and ketoprofen on AZT pharmacokinetics were studied in rats. The influence of AZT on the pharmacokinetics of diclofenac or ketoprofen was also investigated. The administration of diclofenac (3 mgkg(-1)) or ketoprofen (1 mgkg(-1)) did not significantly alter AZT (1.5 mgkg(-1)) pharmacokinetic parameters compared with administering AZT alone. There was no significant difference between the pharmacokinetics of ketoprofen given alone or in combination with AZT. However, the co-administration of AZT with diclofenac affected the pharmacokinetics of diclofenac. The Cmax of diclofenac was significantly (P < 0.05) increased by approximately threefold within a shorter time (0.6+/-0.2 h). The mean AUC value for diclofenac was increased from 2.29 to 5.04 microg mL(-1) h in the presence of AZT. AZT decreased the mean apparent clearance of diclofenac by 54%. The increase in diclofenac concentrations could be attributed to a decrease in its clearance or delay in its metabolite formation due to a competitive effect. The results show that diclofenac and AZT should be given with caution because of the possible increase of diclofenac toxicity, in anticipation of follow-up clinical studies to examine this finding in man. AZT and ketoprofen could be a safe combination since no pharmacokinetic interaction was detected.

show abstract

“…However, it was concluded that the change was due to an increased absorption rate. [97] From the studies published so far, no final conclusion regarding the interaction between NSAIDs and steroids can be drawn; however, the interaction does not appear to have any clinical relevance. Moreover, although the interaction potential seems unimportant, one has to consider that concurrent administration of corticosteroids and NSAIDs in the elderly is a risk factor in itself for the development of upper gastrointestinal bleeding.…”

Section: 6 Steroid Hormonesmentioning

confidence: 93%

Pharmacokinetic-Pharmacodynamic Drug Interactions with Nonsteroidal Anti-Inflammatory Drugs

Brouwers¹,

Smet

1994

Clinical Pharmacokinetics

View full text Add to dashboard Cite

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.

show abstract

Pharmacokinetics of diclofenac sodium after intramuscular administration in combination with triamcinolone acetate

Cited by 14 publications

References 6 publications

Increased Absorption Rate of Diclofenac from Fast Acting Formulations Containing Its Potassium Salt

Increased Absorption Rate of Diclofenac from Fast Acting Formulations Containing Its Potassium Salt

Zidovudine, Diclofenac and Ketoprofen Pharmacokinetic Interactions in Rats

Pharmacokinetic-Pharmacodynamic Drug Interactions with Nonsteroidal Anti-Inflammatory Drugs

Contact Info

Product

Resources

About