Pharmacokinetics and Pharmacodynamics of Dexamethasone after Intravenous Administration in Camels: Effect of Dose

Katheeri, Nawal A. Al; Wasfi, I.A.; Lambert, Matthew; Saeed, Aysha

doi:10.1023/b:verc.0000040243.30199.1f

Cited by 15 publications

(10 citation statements)

References 35 publications

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“…Consequently, this might suggest that dexamethasone‐induced hydrocortisone suppression also is a graded and not a dichotomous response. Furthermore, a plasma dexamethasone concentration–hydrocortisone response relationship has also been shown in humans and in camels (Mager et al ., ; Al Katheeri et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Plasma concentration‐dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone‐21‐isonicotinate

Ekstrand

Bondesson

Gabrielsson

et al. 2014

Vet Pharm & Therapeutics

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Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half-life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half-life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.

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Section: Discussionmentioning

confidence: 97%

Plasma concentration‐dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone‐21‐isonicotinate

Ekstrand

Bondesson

Gabrielsson

et al. 2014

Vet Pharm & Therapeutics

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“…At the same time, marked increase in glucose levels was observed, which is one of the adverse effect attributed to dexamethasone. The previous study has reported that treatment with dexamethasone increases glucose level by promoting hepatic gluconeogenesis and inhibit its peripheral utilization [26]. The waste product of protein metabolism, urea is eliminated through renal route.…”

Section: Biochemical Analysismentioning

confidence: 99%

Assesment of 28 days repeated adminstration toxicity profile of dexamethasone palmitate injection

Sharma

Rasania

Dadhaniya

et al. 2015

J. Nepal Pharm. Assoc.

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Although, the dexamethasone have been used for the managements, against various ailments as single API or in combination with other drugs as acetate or palmitate salt. However, Dexamethasone as palmitate salt has not been investigated so far for sub acute toxicity on intravenous administration. Therefore, an attempt has been made to investigate sub-acute toxicity of dexamethasone palmitate injection. The drug was administered in experimental animals at different dose levels (0.07, 0.18 and 0.44 mg/kg, b.w.), for 28 days, and alteration in biochemical and haematological parameters was recorded along with histological examinations. The result data revealed that intravenous administration of dexamethasone palmitate does not causes any significant alteration in experimental animals examined at different levels. The observed changes were either well established adverse effects of Dexamethasone or were in laboratory reference range limit. The intravenous administered doses of drug were found safer, although somewhat adverse reactions may be observed at higher dose level (s).

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“…However, clearance of a particular drug may vary considerably among animals, for example meloxicam clearance in camels and horses is 2 and 91 mL·h/kg, respectively; hence, extrapolating dose regimens from one species to the other is not appropriate. This practice, however, was because of the lack of integrated PK/PD modeling of drugs in camels (Al Katheeri et al. , 2004).…”

Section: Discussionmentioning

confidence: 99%

The pharmacokinetics and metabolism of meloxicam in camels after intravenous administration

Wasfi¹,

Ali²,

Agha³

et al. 2011

Vet Pharm & Therapeutics

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The pharmacokinetics and metabolism of meloxicam was studied in camels (Camelus dromedarus) (n = 6) following intravenous (i.v.) administration of a dose of 0.6 mg·kg/body weight. The results obtained (mean ± SD) were as follows: the terminal elimination half-life (t(1/2β) ) was 40.2 ± 16.8 h and total body clearance (Cl(T) ) was 1.94 ± 0.66 mL·kg/h. The volume of distribution at steady state (V(SS)) was 92.8 ± 13.7 mL/kg. One metabolite of meloxicam was tentatively identified as methylhydroxy meloxicam. Meloxicam and metabolite were excreted unconjugated in urine. Meloxicam could be detected in plasma 10 days following i.v. administration in camels using a sensitive liquid chromatography tandem mass spectrometry (LC/MS/MS) method.

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Pharmacokinetics and Pharmacodynamics of Dexamethasone after Intravenous Administration in Camels: Effect of Dose

Cited by 15 publications

References 35 publications

Plasma concentration‐dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone‐21‐isonicotinate

Plasma concentration‐dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone‐21‐isonicotinate

Assesment of 28 days repeated adminstration toxicity profile of dexamethasone palmitate injection

The pharmacokinetics and metabolism of meloxicam in camels after intravenous administration

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