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Microsoft word - obese patients - medication dosing cshp.doc

RQHR Pharmacy Services
Medication Dosing Guidelines in Obese Adults
Adapted and modified from the UWHC Center for Drug with permission.
Wm. Semchuk, M.Sc., Pharm.D., FCSHP
July 2007


A. Introduction
In 2005, 16.4% of the population within the RQHR were identified as being obese. Overweight is defined as a body mass index of 25 to 29.9 kg/m and obesity as a body mass index of 30 kg/m or more. Appropriate drug dosing in the obese patient is a challenge for health care practitioners. Obesity causes physiologic alterations which can affect drug pharmacokinetics. In the obese patient, body composition is characterized by a relatively higher percent of fat and lower percent of water and lean tissue mass than the non-obese patient. In spite of increased cardiac output and total blood volume, the blood flow per gram of fat is less than in the non-obese patient. Histological hepatic changes and an increased glomerular filtration rate have also been reported in obese individuals. Limited kinetic studies have been conducted in the obese, leaving the clinician with few resources to turn to for dosing information. The following guidelines summarize what is known about drug pharmacokinetics in the obese patient and provide dosing information for selected drugs. B. Pharmacokinetic Parameters
1.1 No change in absorption with obese patients. In general, lipid soluble drugs have an increased volume of distribution, but significant exceptions exist. An increased volume of distribution can also result in an increased half-life. t = [(Vd ) x (0.693)] / Cl t = half-life Vd = volume of distribution Cl = clearance The majority of obese patients have a larger amount of lean body mass as well as fat. The lean body mass accounts for 20% to 40% of the excess body weight IBW(males) = 50 kg + 2.3 (height - 60) kg IBW(females) = 45.5 kg + 2.3 (height - 60) kg IBW - ideal body weight in kg Height - inches: 1"=0.0254 m 3.1 Albumin and total protein concentrations are unchanged. 3.2 AAG concentrations may be increased, but changes in acidic drug binding are not clinically 3.3 Lipoproteins, such as cholesterol and triglycerides, are usually increased in obesity, but the clinical significance of these changes on drug binding is unknown. Any PRINTED version of this document is only accurate up to the date this document was developed. RQHR can not guarantee the currency or accuracy of any printed policy. RQHR accepts no responsibility for use of this material by any person or organization not associated with RQHR. No part of this document may be reproduced in any form for publication without permission of RQHR. 4.1 Fatty infiltrates in the liver occur in obese patients. The extent is proportional to the degree of obesity. The correlation between fatty infiltrates and metabolic changes is not well understood. 4.2 Phase I metabolism - oxidation, reduction, or hydrolysis is increased or unchanged in 4.3 Phase II metabolism - glucuronidation and sulfonation can be enhanced and cause an increased clearance of drug. Conjugation of drugs can be increased or unchanged. 4.4 High-extraction elimination - there is no significant difference in hepatic blood flow or 5.1 Drugs eliminated primarily through glomerular filtration have increased renal clearance. Filtered and secreted drugs have increased renal clearance. None of the empirically derived equations correlate well with the actual creatinine clearance in critically ill obese patients. Using IBW underestimates creatinine clearance. Using ABW overestimates creatinine clearance. It is best to obtain a measured creatinine clearance in these patients. Any PRINTED version of this document is only accurate up to the date this document was developed. RQHR can not guarantee the currency or accuracy of any printed policy. RQHR accepts no responsibility for use of this material by any person or organization not associated with RQHR. No part of this document may be reproduced in any form for publication without permission of RQHR. Dosing Wt
Comments
IBW ABW DW
It will take longer to reach steady state in long term therapy, but the final concentration will be similar in obese patients Use ABW for conventional and liposomal amphotericin products Larger volumes of distribution in obese patients Time to reach steady state may be prolonged. Eighteen healthy obese patients with BMI 38.8 ± 6 kg/m and TBW 111.4 ± 19.9 kg were compared to 13 healthy lean patients. Increased clearance with partial distribution to adipose tissue; Dose initially on TBW and adjust subsequent doses based on clinical Study of subjects 18-65 years old: 6 moderately obese (BMI 25-39.9 kg/m ), 6 morbidly obese (>40 kg/m ) and 12 matched controls (matched for age and renal function, BMI 18-24 kg/m ). The AUC was 30% higher in obese patients, but was within the range of safety and tolerated well. Obese patients experience a longer half life. Any PRINTED version of this document is only accurate up to the date this document was developed. RQHR can not guarantee the currency or accuracy of any printed policy. RQHR accepts no responsibility for use of this material by any person or organization not associated with RQHR. No part of this document may be reproduced in any form for publication without permission of RQHR. Dose initially on TBW and adjust subsequent doses based on clinical response. Twenty patients > 135 kg (136-227 kg) were compared to 32 patients < 135 kg (50-133 kg). The assay used to measure plasma concentrations of activated protein C did not distinguish between endogenous activated protein C and drotrecogin. Use TBW up to 150 kg and monitor anti-Xa concentrations (heparin level). Based on one patient with BMI 48.3 kg/m (227 kg) and steady state plasma concentrations. Dose initially on TBW and adjust subsequent doses based on clinical response. Case reports show increased requirements in obesity with a maximum bolus of 10,000 units and infusion rate of 15,000 units/hour Increased volume of distribution and half-life, clearance is about One case report (patient with BMI 89 kg/m suggests using a dosing weight of IBW + 0.27(TBW-IBW). Another study with 7 patients, mean weight 146 ± 37 kg, revealed ↓ concentrations relative to normal-weight people, but inhibitory activity occurred in the serum for each isolate except one (MRSA). Increased volume of distribution and clearance, half-life the same. Monitor concentration in obese patients. Increased volume of distribution and elimination half-life in obese patients. Loading dose based on TBW, maintenance dose based on IBW. Any PRINTED version of this document is only accurate up to the date this document was developed. RQHR can not guarantee the currency or accuracy of any printed policy. RQHR accepts no responsibility for use of this material by any person or organization not associated with RQHR. No part of this document may be reproduced in any form for publication without permission of RQHR. Weight is a significant determinant in pharmacokinetics and it distributes extensively to adipose tissue. Consider doses of 600 mg daily. MD LD Use an adjusted weight of IBW + 1.33(TBW-IBW) for the loading dose Studied in general anesthesia, not ICU sedation Although thiopental distributes to adipose tissue, obese patients may be more sensitive to thiopental. Loading dose based on TBW, maintenance dose based on IBW DW = 0.4(TBW-IBW) + IBW, monitor serum sulfamethoxazole Changes in body weight will affect clearance. Monitor concentrations Loading dose based on TBW, maintenance dose based on IBW Per communication with Pfizer Pharmaceuticals 7/27/04 ABW – actual body weight IBW – ideal body weight Males: 50 kg + 2.3 kg [height (inches) – 60] Females: 45.5 kg +2.3 kg [height (inches) – 60] TBW – total body weight DW – dosing weight for drugs (not for creatinine clearance calculation) LD – loading dose MD – maintenance dose BMI – body mass index AUC – area under the curve MRSA – methicillin resistant staph aureus Any PRINTED version of this document is only accurate up to the date this document was developed. RQHR can not guarantee the currency or accuracy of any printed policy. RQHR accepts no responsibility for use of this material by any person or organization not associated with RQHR. No part of this document may be reproduced in any form for publication without permission of RQHR. C. References
1. Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing in obese patients. Clin Infect Dis 1997;25:112-118. 2. Bauer LA, Blouin RA, Griffen, et al. Amikacin pharmacokinetics in morbidly obese patients. Am J Hosp 3. Bauer LA, Edwards WAD, Dellinger EP, Simonowitz, DA. Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol 1983;24:643-647. 4. Casati A, Putzu M. Anesthesia in the obese patient: pharmacokinetic considerations. J Clin Anaesthesia 5. Caraco Y, Zylber-Katz E, Berry EM, Levy M. Carbamazepine pharmacokinetics in obese and lean subjects. 6. Forse RA, Karam B. MacLean LD, Christou NV. Antibiotic prophylaxis for surgery in morbidly obese patients. 7. Allard S, Kinzig M, Bovin G, et al. Intravenous ciprofloxacin disposition in obesity. Clin Pharm Therap 8. Hollenstein UM, Brunner M, Schmid R, Mueller M. Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing. Inter J Obesity & Related Met Dis 2001;25:354-358. 9. Caldwell JB, Nilsen AK. Intravenous ciprofloxacin dosing in a morbidly obese patient. Ann Pharmacother 10. Falagas ME, Kasiakou SA. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 2005;40:1333-1341. 11. Rosner GL. Hargis JB. Hollis DR, et al. Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541. J Clin Oncology 1996;14:3000-3008. 12. Garcia-Saiz M, Lopez-Gil A, Alfonso I, Boada JN, Armijo JA. Factors influencing cyclosporine blood concentration-dose ratio. Ann Pharmacother 2002;36:193-199. 13. Yee JY, Duffull SB. The effect of body weight on dalteparin pharmacokinetics. A preliminary study. Europ J of Clin Pharmcol 2001;56:293-297. 14. Smith J, Canton EM. Weight-based administration of dalteparin in obese patients. Amer J Health Syst 15. Hirsh J, Raschke R. Heparin and low-molecular weight heparin. Chest 2004;126(3 suppl):188S-203S. 16. Dvorchik, BH, Damphousse D. The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched nonobese subjects. J Clin Pharmacol 2005;45:48-56. 17. Abernathy DR et al. Prolonged accumulation of diazepam in obesity. J Clin Pharmacol 1983:23:369-76. 18. Navarro WH. Impact of obesity in the setting of high-dose chemotherapy. Bone Marrow Transplant 19. Levy H, Small D, Heiselman DE, et al. Obesity does not alter the pharmacokinetics of drotrecogin alfa (activated) in severe sepsis. Ann Pharmacother 2005; 39:262-267. 20. Cohen LG, Dibiasio A, Lisco SJ . Hurford WE . Fluconazole serum concentrations and pharmacokinetics in an obese patients. Pharmacother 1997;17:1023-1026. 21. Altamura AC, Moro AR, Percudani M. Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 22. Schwartz SN, Pazin GJ, Lyon JA, et al. A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J Infect Dis 1978;138;499-505. 23. Jaber LA, Ducharme MP, Halapy H. The effects of obesity on the pharmacokinetics and pharmacodynamics of glipizide in patients with non-insulin dependent diabetes mellitus. Therap Drug Monitor 1996;18:6-13. Any PRINTED version of this document is only accurate up to the date this document was developed. RQHR can not guarantee the currency or accuracy of any printed policy. RQHR accepts no responsibility for use of this material by any person or organization not associated with RQHR. No part of this document may be reproduced in any form for publication without permission of RQHR. 24. Ellison MJ, et al. Calculation of heparin dosage in morbidly obese woman. Clin Pharmacokinet 1989; 8:65- 25. Spruill WJ, Wade WE, Huckaby WG, Leslie RB. Achievement of anticoagulation by using a weight-based heparin dosing protocol for obese and nonobese patients. Am J Health-Sys Pharm 2001;58:2143-2146. 26. Lind MJ, et al. Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution. Cancer Chemo Pharm 1989;25:139-142. 27. Refludan, 2005 package insert Berlex Labs. 28. Mersfelder TL, Smith CL. Linezolid pharmacokinetics in an obese patient. Am J Health-Syst Pharm 29. Stein GEW, Schooley SL, Peloquin CA, et al. Pharmacokinetics and pharmacodynamics of linezolid in obese patients with cellulitis. Ann Pharmacother 2005;39:427-432. 30. Reiss RA, et al. Lithium pharmacokinetics in the obese. Clin Pharmacol Therap 1994;55:392-398. 31. Fleming RA, Eldridge RM. Johnson CE. Stewart CF. Disposition of high-dose methotrexate in an obese cancer patient. Cancer 1991;68:1247-50. 32. Dunn TE, Ludwig EA. Slaughter RL, et al. Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. Clin Pharmacol Ther 1991;49:536-549. 33. Sullivan JT, Woodruff M, Lettieri J. Pharmacokinetics of once-daily moxifloxacin (Bay6 12-8039), a new enantiomerically pure 8-methoxy quinolone. Antimicrob Agents & Chemother 1999;43:2797-2797. 34. Rodvold KA, Neuhauser M. Pharmacokinetics and pharmacodynamics of fluoroquinolones. Pharmacotherapy 2001; 21:233S-252S. 35. Yuk J, Nightingale CH, Sweeney K, et al. Pharmacokinetics of nafcillin in obesity. J Infect Dis 36. Wilkes L, et al. Phenobarbital pharmacokinetics in obesity. A case report. Clin Pharmacokinet 1992; 37. Kuranari M, Chiba S, Ashikari Y, et al. Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study. J Clin Pharm Ther 1996;21:83-7. 38. Abernethy DR Greenblatt DJ. Phenytoin disposition in obesity: determination of loading dose. Arch Neurol 39. Servin-Farinoi R, Haberer JP, et al. Propofol infusions for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide: a clinical and pharmacokinetic study. Anesthesiology 1993;78:657-665. 40. Dohm GL, et al. Pharmacokinetics of ranitidine in morbidly obese women. Drug Intel Clin Pharm 41. Geisler PJ, Manis RD, Maddus MS. Dosage of antituberculosis drugs in obese patients. Am Rev Respir Dis 42. Puhringer FK, Keller C. Kleinsasser A, et al. Pharmacokinetics of rocuronium bromide in obese female patients. Eur J Anaesthesiol 1999;16:507-520. 43. Poirier JM, LeJeune C, Cheymol G, et al. Comparison of propranolol and sotalol pharmacokinetics in obese subjects. J Pharm Pharmacol 1990;42:344-348. 44. Zahorska-Markiewicz B, et al. Pharmacokinetics of theophylline in obesity. Int J Clin Pharmacol Therap 45. Blouin RA, Bauer LA, Miller DD, et al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother 1982; 21:575-580. 46. Ducharme MP, Slaughter RL, Edwards DJ. Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight. Ther Drug Moni 1994; 16:513-518. 47. Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol 1995; 48. Vance-Bryan K, Guay DR, Gilliland SS, et al. Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique. Antimicrob Agents & Chemother 1993; 37:436-40. Any PRINTED version of this document is only accurate up to the date this document was developed. RQHR can not guarantee the currency or accuracy of any printed policy. RQHR accepts no responsibility for use of this material by any person or organization not associated with RQHR. No part of this document may be reproduced in any form for publication without permission of RQHR. 49. Schwartz AE, et al. Pharmacokinetics and pharmacodynamics of vecuronium in the obese surgical patient. Anesthesia Analgesia 1992;74:515-18. 50. Absher RK, Moore ME, Parker MH. Patient-specific factors predictive of warfarin dosage requirements. Ann Pharmacotherap 2002;26:1512-1517. 51. Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients. Clin Pharmacokinet 52. Cheymol G. Effects of obesity on pharmacokinetics. Implications for drug therapy. Clin Pharmacokinet 53. Green B, Duffull ST. What is the best size descriptor to use for the pharmacokinetic studies in the obese? Br J Clin Pharmacol 2004;58:119-133. 54. Devine BJ. Case number 25: Gentamicin therapy. Drug Intell Clin Pharm 1974;8:650-655. 55. Erstad BL. Which weight for weight-based dosage regimens in obese patients? Am J Health-Syst Pharm 56. Cheymol G, Effects of obesity on pharmacokinetics. Implications for drug therapy. Clin Pharmacokinet 57. Abernethy DR, GreenBlatt DJ. Drug disposition in obese humans. An update. Clin Pharmacokinet 58. Spinler SA, Nawarskas JJ, Boyce EG, et al. Predictive performance of ten equations for estimating creatinine clearance in cardiac patients. Ann Pharmacother 1998;32:1275-1283. 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