8051373d7c09463d29b0fd561fe1f775.ppt
- Количество слайдов: 21
Clinical Pharmacokinetics of VANCOMYCIN Mohd Bin Makmor Bakry, Ph. D, RPh Senior Lecturer in Clinical Pharmacy Faculty of Pharmacy Universiti Kebangsaan Malaysia Kuala Lumpur
INTRODUCTION • • Inhibits bacterial cell wall synthesis Time-dependent effect Gram positive bacteria Indications : • Documented infections: • • Methicillin/Cephalosporin-Resistant Staphycoccal infection. Penicillin/Cephalosporin-Resistant Streptococcal infection. Staphy. /Strep. infection in patient allergic to penicillin. Staphy. infection in patient with renal disease undergoing hemodialysis. • Penicillin-Resistant Diphtheroid infection. • Severe antibiotic-associated enterocolitis.
• Indications (cont’) : • Empiric Therapy: • • • Suspected MRSA nosocomial infection. Meningitis in patient who had neurosurgery. Neutropenic febrile patient not responding or allergic to penicillin. • Suspected Staphy. infection in patient with renal disease undergoing hemodialysis. • Prophylaxis: • Endocarditis in patient allergic to penicillin. • Prosthetic valve placement in patient allergic to penicillin.
ADVERSE DRUG REACTION • • Ototoxicity (tinnitus, fullness in the ear) Nephrotoxicity • An increase in Sr. Cr of 0. 5 mg/d. L or greater, or as 50% increase from baseline. • Occurs at a rate of 5% with Vancomycin alone and increase to 22% with addition of Aminoglycosides. • Red-Man Syndrome (hypotension, upper body • Cutaneous reaction (urticaria, angioedema, erythema) Neutropenia (within 15 – 30 days of drug initiation) Fever • • maculopapular rash)
PHARMACOKINETIC CHARACTERISTICS • • Two- or three-compartment model. Bioavailability • Per oral < 5% • Intravenous 100% • • Protein binding 30 – 55% Excretion • Renal: >90% unchanged in urine
KEY PARAMETERS • Ctarget • F Vd CLVanco t½ Ke • • Conventionally P = 40 – 50 mg/L T = 10 – 15 mg/L Continuous infusion Cavess = 12 – 18 mg/L <0. 05 PO 0. 7 (0. 5 – 1. 0) (L/kg) 0. 65 CLCr x 0. 06 (L/H) 7 (H) 0. 00083(CLCr) + 0. 0044 (H-1) *CLCr in ml/min
INITIATING VANCOMYCIN • Cultures • Appropriate C&S obtain within 48 hrs before starting therapy. • Antibiotic therapy modified (if necessary) within 24 hrs of the C&S results. • Renal Function • Estimated CLCr within 24 hrs of initiating therapy. • Monitoring CLCr every 3 – 5 days during therapy.
INITIATING VANCOMYCIN (CONT’) • Dosage Regimen & Monitoring Needs • Conventional dosing • Peak & Trough concentration method • Continuous infusion • Trough concentration method
INITIATING VANCOMYCIN (CONT’) • Conventional Dosage Regimen • • • Initial per dose is between 10 – 15 mg/kg body wt Dosage interval based on estimated CLCr. Rate of infusion not more than 20 mg/min. Adjustment based on measured levels. Serum Drug Concentration • • Levels taken at steady-state. If stable renal function, repeat trough levels once a week. Trough levels obtained if with other nephrotoxic drugs. Trough and peak levels obtained if: • Not responding to therapy. • Altered physiologic parameters
INITIATING VANCOMYCIN (CONT’) • Continuous Infusion Regimen • Infusion rate is based on estimated CLCr and targeted Cavess (15 mg/L). • Rate of infusion, Ro (mg/H) Ro = CLvanco. Cavess = Vd. Ke. Cavess • Adjustment based on measured Cavess
• Lake’s Method INITIATING VANCOMYCIN (CONT’) • Target serum levels: T = 5 – 10 mg/L (30 min before the next infusion) P = 20 – 30 mg/L (15 min after the end of infusion) • Maintenance dose (per dose) = 8 mg/kg (LBW) • To be give at Q H interval: CLCr (ml/min) (H) >90 6 70 – 89 8 46 – 69 12 30 – 45 18 15 – 29 24
INITIATING VANCOMYCIN (CONT’) • Rodvold’s Method • Target serum levels: T = 5 – 10 mg/L (30 min before the next infusion) P = 30 – 40 mg/L (15 min after the end of infusion) • Daily maintenance dose Dose (mg/kg TBW per 24 H) = (0. 227(CLCr) + 5. 67 • Interval: CLCr (ml/min) >65 46 – 65 20 – 39 10 – 19 (H) 8 12 24 48
ADJUSTING THE DOSAGE REGIMEN ln Cp Cmax Cpostdose C*predose ti Ct, max C* Cmin t
ADJUSTING THE DOSAGE REGIMEN (CONT’) • Sawchuck-Zaske Method (Conventional/Multiple short infusion) • Determine the t½ Ke = ln (Cpeak/Ctrough) / (ttrough – tpeak) t½ = 0. 693 / Ke • Determine the Vd Vd = R o x 1 – e-Keti. Ke (Cmax – (Cmine-Keti) *Ro = mg/H infusion • Determine the new = ln (Cmax desired / Cmin desired) + ti Ke
ADJUSTING THE DOSAGE REGIMEN (CONT’) • Sawchuck-Zaske Method (cont’) • Determine the Ronew ( ) Ronew = Ke Vd Cmax desired x 1 – e-Keti • Predict Ct, max at t after the end of infusion and Cmin Ct, max = Ro x 1 – e-Keti x e-Ket Ke (Cmax – (Cmine-Ke ) Cmin = Ct, maxe-Ke( - (ti – t)
ADJUSTING THE DOSAGE REGIMEN (CONT’) • Continuous Infusion Method • Determine the CLvanco* = Ro / achieved Cavess • Determine the new Ro (mg/H) Ro = CLvanco* x targeted Cavess
EXAMPLE OF CASES CASE 1 • Mr. AD, 62 years old patient was diagnosed to have MRSA and allergic to penicillin, Body weight is 98 kg and height is 165 cm. Lab results: Sr. Cr 95 mol/L, Urea 8. 5 Suggest the best Vancomycin dosage regimen to achieve Cpeak = 40. 0 mg/L and Ctrough = 10. 0 mg/L. Estimate the dose to be given through continuous infusion, Cp = 15 mg/L
CASE 2 • Mrs. PS, 55 years old patient was diagnosed to have MRSA sepsis. Body weight is 85 kg and height is 170 cm. Given Short Inf. for 0. 5 H Vancomycin 500 mg Q 8 H Lab results: C&S S. aureus. , Sr. Cr 150 mol/L, Urea 9. 2, Cpeak = 40 mg/L, Ctrough = 24. 0 mg/L Adjust the Vancomycin dose regimen to achieve Cpeak = 40. 0 mg/L and Ctrough = 10. 0 mg/L.
CASE 3 • Mrs. SP, 40 years old patient was diagnosed to have endocarditis and allergic to penicillin. Body weight is 45 kg and height 165 cm. Given Short Inf. for 1 H Vancomycin 750 mg Q 12 H Lab results: C&S S. aureus. , Sr. Cr 120 mol/L, Urea 9. 0, Cpeak = 30 mg/L, Ctrough = 22. 0 mg/L The doctor would like to change the method of administration to continuous infusion for 24 hours and targeted Cp = 15 mg/L. Suggest new dosage regimen to reach this later target and when to start this new regimen?
CASE 4 • Mr. IZ, 50 years old patient was diagnosed with Co. NS and allergic to penicillin. Body weight is 60 kg and height 150 cm. Given continuous infusion of Vancomycin 80 mg/H Lab results at day 3: Sr. Cr 200 mol/L (120 mol/L at D 1), Cave = 26. 0 mg/L The doctor would like to change the method of administration to conventional method and targeted Ctrough = 10 mg/L. Suggest new dosage regimen to reach this later target and when to start this new regimen?
THANK YOU
8051373d7c09463d29b0fd561fe1f775.ppt