Dexamethasone elimination

Lenalidomide, a derivative of thalidomide, was introduced in 2004. Patients with multiple myeloma stage II/III, who have undergone at least one previous treatment can be treated with bortezomib or with lenalidomide in combination with dexamethasone. There is good oral absorptin with peak plasma levels at 0.5-4 hours. Lenalidomide is maily eliminated by the kidneys with a half-life of circa 3-9 hours. Teratogenicity cannot be excluded. Side effects include thrombosis, pulmonary embolus, and hepato-toxicity, as well as bone marrow toxicity resulting in neutropenia and thrombocytopenia. 

Residue depletion studies indicated that different formulations led to different dexamethasone depletion rates. Studies in cattle and pigs indicated that dexa-methasone residues were quickly eliminated from muscle and milk of cows. Residues did not occur in the free form in fat, whereas the depletion rate in liver was the slowest. Following intramuscular administration of 60 g/kg bw to cows, mean dexamethasone levels in milk declined from 8.4 ppb at the first milking after treatment to below 1 ppb at the sixth milking after treatment (52). 

The drug particle size plays the most important role in the formulation process of suspensions. Particles greater than 10 pm cause patient discomfort. As they are perceived as foreign substances, they cause reflex tearing in order to eliminate the particles from the ocular surface [176]. A study by Schoenwald and Stewart [177] showed the influence of the particle size of dexamethasone on its bioavailability. The in vivo dissolution rate decreased with increasing particle size to the point when particles were removed from the conjunctival sac before the dissolution was complete. 

VINCA ALKALOIDS - VINBLASTINE, VINCRISTINE 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 of plasma concentrations of vinblastine and vincristine, with risk of inadequate therapeutic response. Reports of 1 AUC by 40% and elimination half life by 35%, and t clearance by 63%, in patients with brain tumours taking vincristine, which could lead to dangerously inadequate therapeutic responses Due to induction of CYP3A4-mediated metabolism Monitor for clinical efficacy, and t dose of vinblastine and vincristine as clinically indicated in the latter case, monitor clinically and radiologically for clinical efficacy in patients with brain tumours and t dose to obtain desired response... 

Intravitreal application of dexamethasone may reduce the elimination of intravitreal vancomycin and may enhance this therapy, as suggested by an in vivo study in rabbits (120). 

Park SS, Vallar RV, Hong CH, von Gun ten S, Ruoff K, D Amico DJ. Intravitreal dexamethasone effect on intra-vitreal vancomycin elimination in endophthalmitis. Arch Ophthalmol 1999 117(8) 1058-62. 

The dominant path of distribution and elimination in the vitreous depends on a molecule s physicochemical properties and its substrate affinity. Lipophilic compounds, such as fluorescein (250) or dexamethasone (251), and compounds subject to active transport mechanisms, tend to be eliminated via the retina (Fig. 16). On the other hand, hydrophilic substances, such as fluorescein glucuronide, and compounds with poor retinal permeability, such as fluorescein dextran, tend to exit the vitreous anteriorly through the hyaloid membrane into the posterior chamber and subsequently into the anterior chamber, where they are subject to elimination pathways for aqueous humor (250). In general, shorter vitreal half-lives are associated with elimination through the retina, with its high surface area, whereas longer half-lives are indicative of elimination through the hyaloid membrane. 

Brain abscess formation was studied experimentally in rats, and treatment with different combinations of hyaluronidase, dexamethasone, and antibiotic has been investigated [128]. The results showed that combined therapy with antibiotic and hyaluronidase, started the day before inoculation, averted the formation of brain abscess and the therapy, started after encapsulation, effectively eliminated the organisms. However, the same therapy started at the cerebritis stages caused an increase of cerebritis. 

Pemetrexed toxicity mirrors that of methotrexate, with the additional feature of a prominent erythematous and pruritic rash in 40% of patients. Dexamethasone, 4 mg twice-daily on days —1, 0, and +1, markedly diminishes this toxicity. Unpredictably severe myelosuppression with pemetrexed, seen especially in patients with preexisting homocystinemia and possibly reflecting folate deficiency, is largely eliminated by concurrent administration of low doses o/folic acid, 0.35—1 mg/day beginning 1—2 weeks prior to pemetrexed and continuing while the drug is administered. Intramuscular vitamin Bj2(I mg) is given with the first dose of pemetrexed to correct possible Bj2 deficiency. There is no evidence that these small doses of folate and Bj compromise the therapeutic effect. 

Formation of the m/e 343 diagnostic fragment was attributed to a facile trans-elimination of water from dexamethasone followed by cleavage of the allylic C2o C2j bond. It is quite conceivable that initial elimination of water occurred under thermal stress rather than under electron impact alone in the reported data. ... 

B.T. assay procedure. A tabulation of a number of such interferences is given in Reference 39. Both positive and negative interferences are possible. The former are due to agents which are oxidized under the conditions of the B.T. reaction. The latter are agents which can alter the pH of the alkaline B.T. reaction mixture thereby decreasing the extent of color formation. Effective elimination of interferences can often be achieved by selective extraction and chromatographic procedures. An automated B.T. assay has been described for dexamethasone tablets. ... 

Uncertain. Dexamethasone is an inducer of the cytochrome P450 isoenzyme CYP3A4, and might therefore be expected to reduce levels of albendazole, so the finding is unexpected. Dexamethasone appears not to alter the rate of formation of albendazole sulfoxide, but decreases its elimination. ... 

A study in 8 healthy subjects found that itraconazole 200 mg daily for 4 days increased the AUC, peak plasma level, and elimination half-life of a single 4.5-mg dose of dexamethasone by 3.7-, 1.7-, and 2.8-fold, respectively. In another phase of the study itraconazole decreased the systemic clearance of intravenous dexamethasone 5 mg by 68% and increased the AUC and elimination half-life 3.3- and 3.2-fold, respectively. The adrenal-suppressant effects of dexamethasone were enhanced by itraconazole. ... 

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