Dexamethasone pharmacokinetics

Docetaxel, another taxane, binds to tubulin to promote microtubule assembly. The pharmacokinetics of docetaxel are best described by a three-compartment model, with an a half-life of 0.08 hours, a 3 half-life of 1.6 to 1.8 hours, and a terminal half-life of 65 to 73 hours.14 Docetaxel has activity in the treatment of breast, non-small cell lung, prostate, bladder, esophageal, stomach, ovary, and head and neck cancers. Dexamethasone, 8 mg twice daily for 3 days starting the day before treatment, is used to prevent the fluid retention syndrome associated with docetaxel and possible hypersensitivity reactions. The fluid... 

Other agents such as actinomycin D, C-Myc antisense, dexamethasone, and matrix metalloproteinase inhibitors, aimed at altering inflammatory and smooth muscle actions in the biological repair response to vascular injury, are being evaluated. The success of these devices depends upon multiple issues, including stent platform, carrier, drug properties, and pharmacokinetic profile (18-26). Large randomized, controlled trials, demonstrate a restenosis rate of 5% to 10% with DES (27). 

Pharmacokinetic studies revealed rapid systemic absorption after intramuscular administration of dexamethasone, with peak plasma levels attained at 0.5 h and 6 h in dogs and rats, respectively. It is rapidly excreted in urine and feces. Its biotransformation profile is comparable in rats and humans and mainly involves hydroxylation to 6-hydroxy- and 2-dihydroxy-derivatives followed by conjuga-... 

Takayanagui OM, Lanchote VL, Marques MP, Bonato PS. Therapy for neurocysticercosis pharmacokinetic interaction of albendazole sulfoxide with dexamethasone. Ther Drug Monit 1997 19(l) 51-5. 

McCrea JB, Majumdar AK, Goldberg MR, Iwamoto M, Gargano C, Panebianco DL, Hesney M, Lines CR, Petty KJ, Deutsch PJ, Murphy MG, Gottesdiener KM, Goldwater DR, Blum RA. Effects of the neurokininl receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. Clin Pharmacol Ther 2003 74 17-24. 

Melgert et al. studied the delivery of the corticosteroid dexamethasone to fibrotic livers [240], Dexamethasone has more potent and broader anti-inflammatory effects compared with naproxen. It inhibits the release of inflammatory mediators like TNF-a, IFN-y, and IL-6 and acts as an NFkB inhibitor [241, 242], Dexamethasone coupled to albumin (Dexa-HSA) was specifically taken up by sinusoidal cells in fibrotic rat livers, whereas dexamethasone itself was mainly taken up by hepatocytes. In vivo, Dexa-HSA promoted survival in endotoxin-induced liver inflammation in rats [240], In vitro, anti-inflammatory effects of the conjugate were measured in endotoxin-challenged liver slices. Dexa-HSA inhibited the release of nitric oxide and TNF-a in a dose-dependent manner (Melgert et al. unpublished data). To further enhance the delivery to KC at present dexamethasone is coupled to manHSA, and this conjugate is studied with respect to the pharmacokinetic profile and pharmacotherapeutic effects in fibrotic rats. 

Hansen, D.K., J.B. LaBorde, K.S. Wall, R.R. Holson, and J.F. Young. 1999. Pharmacokinetic considerations of dexamethasone-induced developmental toxicity in rats. Toxicol. Sci. 

Factors contributing to the reduced propensity of some steroids to raise lOP could include their intraocular bioavailability, considerably shorter pharmacokinetic half-life, and greater susceptibility to metabolism as compared with dexamethasone and prednisolone. In addition to the individual steroid s effect on lOP, concentration, frequency, and length of administration may play a role in lOP elevation. 

There are no published reports on the pharmacokinetics of the thiazide-type diuretics in horses. A bolus dose of a combination of dexamethasone (5 mg) and trichlormethiazide (200 mg), a product commonly used for treatment of udder edema in periparturient cattle, is occasionally used to treat edema in horses and there are anecdotal reports that it is efficacious. Hydrochlorothiazide (0.5- 0.7mg/kg orally twice daily) has also been used to enhance urinary potassium excretion and thereby limit the increase in serum potassium concentrations during an episode of hyperkalemic periodic paralysis in horses (Beech Lindborg 1996, Spier et al 1990 see Ch. 8). However, hydrochlorothiazide was less effective than acetazolamide (see below) and phenytoin in controlling the clinical signs, but it did limit the increase in the serum potassium ion concentrations during an oral potassium chloride challenge test (Beech Lindborg 1996). 

Dexamethasone (Decadron) Route Pregnancy Pharmacokinetic Absorbed ... 

L, Mol CA, Borst P. 1995. Absence of the mdrla P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J. Clin. Invest. 96 1698-705... 

Yumoto R, Murakami T, Sanemasa M, Nasu R, Nagai J, Takano M. Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone. Drug Metab Dispos 2001 29(2) 145-151. 

Fialho and Silva-Cunha [127] recently reported formulation of dexamethasone loaded microemulsion based on Cremophore EL, propylene glycol and IPM. The tolerability of the microemulsions was established and it did not cause any significant alteration to eyelids, conjuctiva, cornea and iris. The pharmacokinetics of the dexamethasone from microemulsions was compared to the marketed formulation in rabbit eye. The microemulsion formulation acted faster as well as for the longer period of time (Fig. 9.6 and Table 9.7). 

Table 9.7 Ocular pharmacokinetics of dexamethasone in various formulations...

Kwak HW, D Amico DJ. Evaluation of the retinal toxicity and pharmacokinetics of dexamethasone after intravitreal injection. Arch Ophthalmol 1992 110 259-266. 

Ulrich, B. Frey, F.J. Speck, R.F. Frey, B.M. Pharmacokinetics/pharmacodynamics of ketoconazole-prednisolone interaction. J.Pharmacol.Exp.Ther, 1992, 260, 487-490 [mouse plasma dexamethasone (IS) LOD 10 ng/mL extracted prednisolone]... 

Rose, J.Q. Jusko, W.J. Corticosteroid analysis in biologiced fluids by high-performance liquid chromatography. J.Chromatogr., 1979, 162, 273-280 [plasma urine saliva extracted hydrocortisone, prednisolone dexamethasone (IS) LOD 5 ng/mL pharmacokinetics simultaneous beclomethasone, meth-ylprednisolone, trieuncinolone acetonide]... 

A. Prototypes and Pharmacokinetics All of the corticosteroids are potentially beneficial in severe asthma (see Chapter 39). However, because of their toxicity, systemic (oral or intravenous) corticosteroids are used only if other therapies are unsuccessful. In contrast, local aerosol administration of surface-active corticosteroids (eg, beclomethasone, budesonide, dexamethasone, flunisolide, fluticasone, mometasone) is relatively safe inhaled corticosteroids have become common first-line therapy for individuals with moderate to severe asthma. 

Modification of the pharmacokinetics through structural alterations has provided several new steroids with a better GR affinity and therapeutic index and a lower bioavailability than the older drugs (Fig. 33.14). The new inhaled/intranasal glucocorticosteroids like mometasone furoate, budesonide and fluticasone propionate are more lipophilic than those used in oral and systemic therapy and have greater affinity for the GR than does dexamethasone as a consequence of their greater lipophilicity (43). Several of the topical corticosteroids, such as mometasone furoate, BDP, triamcinolone acetonide, and flunisolide, were reintroduced as inhalation and intranasal dosage forms for treatment of respiratory diseases (e.g., asthma or rhinitis). Inhaled budesonide and flunisolide are readily absorbed from the airway mucosa into the blood and are rapidly biotransformed in the liver into inactive metabolites. Mometasone furoate and fluticasone propionate are very potent anti-inflammatory steroids with an oral bioavailability of less than 1%. Obviously, the risk of systemic side effects for these newer corticosteroids is greatly reduced when compared with ... 

Rohdewald P, Moiimann H, Barth J, et al. Pharmacokinetics of dexamethasone and its phosphate ester. Biopharm Drug Dispos 1987 8 205-212. 

Kovarik JM, Purba HS, Pongowski M, Gerbeau C, Humbert H, Mueller EA. Pharmacokinetics of dexamethasone and valspodar, a P-glycoprotein (mdrl) modulator implications for coadministration. Pharmacotherapy 1998 18 1230-1236. 

Information seems to be limited but the pharmacokinetic interaction would appear to be established. Just how much it affects the outcome of treatment for systemic worm infections such as cysticercosis is unknown because the optimum praziquantel levels are still uncertain, and it is possible that the metabolites of praziquantel might be active. The authors of one report suggest that dexamethasone should not be given continuously with praziquantel but only used transiently to resolve inflammatory reactions to praziquantel treatment. Alternatively, limited information suggests the addition of cimetidine may allow dexamethasone to be used. Intravenous methylprednisolone has also been used for acute corticosteroid therapy with praziquantel, and oral prednisone has been used longterm to prevent further tissue damage associated with inflammation but the effect of these corticosteroids on the plasma levels of praziquantel do not appear to have been studied. 

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