Ciprofloxacin Pharmacokinetics in Clinical Canine Patients
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cells may lose their sensitivity to glucocorticoids , complicating medical management . In people , one theory to explain reduced T cell sensitivity to glucocorticoids is the effect of IL-2 . In people , lymphocytes are an important physiological source of melatonin , as they can synthesize and release large quantities of melatonin . Lymphocyte-derived melatonin appears to be directly linked to the release of IL-2 . IL-2-induced glucocorticoid resistance through stimulation of opioid cytokines in T lymphocytes and / or direct inhibition of glucocorticoid receptor expression has been documented in people . 5 Should a similar process of glucocorticoid resistance occur in dogs and cats , concurrent use of cyclosporine may be of logical benefit . Cyclosporine inhibits IL-2 and interferon gamma production through calcineurin inhibition . As veterinarians , we still have a tremendous amount to
Ciprofloxacin Pharmacokinetics in Clinical Canine Patients
Summarised by Dr L L van der Merwe BVSC MMedVet ( Med ) Papich , MG ( 2017 ) Ciprofloxacin Pharmacokinetics in Clinical Canine Patients . Journal of Veterinary Internal Medicine Vol 31 : 1508-1513
Why they did it ? Ciprofloxacin generic tablets for humans are frequently administered to dogs for treatment of bacterial infections because they are inexpensive and readily available . However previous studies have indicated low and variable oral absorption in healthy research dogs ( beagles and greyhounds ). Oral absorption may be as low as 42 % and in a recent study the mean was 58 % but with a high variability and a co-efficient of variation ( CV ) of 45.4 %. The variable absorption appeared to be caused by incomplete and inconsistent dissolution of the generic tablet formulated for use in humans . The objective of this study was to assess the current ciprofloxacin regimens in their ability to reach the recommended pharmacokinetic-pharmacodynamic ( PK / PD ) targets when administered PO to clinical patients .
What they did ? A prospective population pharmacokinetic study was cxonducted using non linear mixed effects modelling . Tablets were dosed intact ( 250mg , 500mg and 750 mg ) at a PO dose as close to 25 mg / kg oid as possible . Four blood sampling events were scheduled . Examination of co-variate plots indicated that the effect of weight on volume of distribution was the most likely factor contributing to between subject variation . learn about melatonin . Unquestionably , research regarding its use in our patients with immune-mediated diseases is needed .
References
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2 . Todisco M , Casaccia P , Rossi N . Severe bleeding symptoms in refractory idiopathic thrombocytopenia purpura : a case successfully treated with melatonin . Am J Ther2003 ; 10:135-136 .
3 . Zhou LL , Wei W , Si JF , et al . Regulatory effect of melatonin on cytokine disturbances in the pristane-induced lupus mice . Mediators Inflamm 2010 . Epub .
4 . Maestroni GJ , Covacci V , Conti A . Hematopoietic rescue via T-cell-dependet , endogenous granulocyte-macrophage colony-stimulating factor induced by the pineal neurohormone melatonin in tumor-bearing mice . Cancer Res 1994 ; 45:2429-2432 .
5 . Walker KB , Potter JM , House AK . Interleukin 2 synthesis in the presence of steroids : a model of steroid resistance . Clin Exp Immunol 1987 ; 68:162-167 .
What they found . Elimination t ½ was 4.35 hours , AUC 13,82 ug . h / mL , and peak concentration ( Cmax ) 1.19ug / mL . these results differed from those of a healthy research Beagle dogs where T1 / 2 was 2.6 hrs , AUS was 22.5ug . h / mL and Cmax was 4.4ug / mL . Similar differences were observed between healthy volunteers and clinically ill human patients .
What is means . Dosage recommendations for ciprofloxacin in dogs vary from 5 – 15 mg / kg po BID to 20 – 25 mg / kg po OID . The most recent study in beagles indicates that an average dose of at least 25mg / kg OID is needed to meet the MIC of 0.25ug / mL . This study showed that with a PO dose of 25mg / kg the target can be met for bacteria with a MIC of ≤ 0.06 µ g / mL . This is not a very high level – i . e . the bacteria would have to be very susceptible . In humans the susceptibility breakpoint is set at 1.0 µ g / mL . Based on the data presented in this trial at this dose there is essentially a 0 % chance that the PK / PD target can be met for bacteria with a MIC of 1.0 µ g / mL for ciprofloxacin . Although many bacteria of Enterobacteriaceae are highly susceptible with ciprofloxacin MIC ≤0.06 µ g / mL , the bacteria that cause resistant infections in dogs such as Staphylococcus spp and Pseudomonas aeruginosa have ciprofloxacin MICs typically > 0.06 µ g / mL .
One of the covariates in the analysis which contributed to variability of volume of distribution was the size ( weight ) of the dog . The result of a larger volume of distribution is a correspondingly lower drug plasma concentration . This has a large impact on the use of this drug as one of the reasons ciprofloxacin is selected is to decrease the expense of treating large dogs , the very animals which show the lower absorption of PO medication and greatest variability in attaining serum comcentrations .
Conclusion : Human generic ciprofloxacin , dosed at 25 mg / kg oid only reached a low MIC of 0.06 µ g / mL , which would be insufficient in the more resistant bacteria and would also show a greater PK / PD variability in larger breed dogs due to a increased volume of distribution with resultant lower serum levels . vet360
Issue 05 | OCTOBER 2017 | 28