TDM aminoglycoside (2022)

Example Half-life, Vd, Clearance 0.693 ������1/2 = (0.085 h−1) = 8.15 hrs = 7.35 L . CL= (K)(Vd) = 0.085x 7.35 = 0.625 L/hr 3. Chose the new steady state peak and trough concentrations For this example, the desired steady state peak and trough are approximately 20 mg/L and 1.5 mg/L , respectively. 30/09/65 51

Example 4. Determine the new dosage interval for the desired concentrations. the dosage interval () is computed using the following equation and a 1-hour infusion time(t’): 5. Determine the new dosage interval for the desired concentrations. The dose is computed following one compartment model intravenous infusion equation used 30/09/65 52

Example 1.5 mg/L 7.35L 1−e ( h−1 ) −1)( ) (. = 131.33 mg , round = 130 mg ( ) ( . )( ) = 152.27 mg , round = 150 mg 30/09/65 53

Therapeutic range and evidence base Table 4 Targeted range following multiple dose therapy for aminoglycosides Drug Trough Peak concentration concentration Amikacin Gentamicin (mg/L) (mg/L) Netilmici <5 15-20 Tobramycin <2 4-12 <2 4-12 <2 4-12 30/09/65 54

Therapeutic range and evidence base 30/09/65 55

Therapeutic range and evidence base The reasons for request  Appropriate of dosing  Ototoxic or nephrotoxic are suspected 30/09/65 56

Therapeutic range and evidence base Factors affecting therapeutic range including important drug interaction  Drug that change fluid balance  Other drug interaction 30/09/65 57

Therapeutic range and evidence base Why are pre and pose dose aminoglycoside concentration is difficult to interpret? • Although we are assured that aminoglycosides concentration being within the target range but the dose may still inappropriate. What must we exclude before conclude appropriateness • Pre-dose <1mg/L Dose interval is acceptable? Was the previous dose obmitted and not given at all? Was an incomplete dose given previously? 30/09/65 58

Therapeutic range and evidence base Pre-dose > 2mg/L Need to extend dosing interval? Was the previous dose given late and thus not a true trough ? Was the sampling obtain early? Was it sample from an admission line.? 30/09/65 59

Therapeutic range and evidence base Post-dose peak within target range Appropriate dose and frequency? Or was an incorrect dose? Was an incorrect dose sample time or method of administration used? Was a toxic dose sample late? 30/09/65 60

Therapeutic range and evidence base • Post-dose peak is above target range – Dose too high? – Was the sample taken before complete distribution? – Was the sample taken from an administration line? 30/09/65 61

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Source: Am Fam Physician. 1998 Nov 15;58(8):1811-1820. 64 30/09/65

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Aminoglycoside nomogram Prototype is Hartford Nomogram 30/09/65 69

Aminoglycoside nomogram Data based on population kinetics for 4 mg/kg (lower line) and 7 mg/kg (upper line). 30/09/65 70

Aminoglycoside analysis HPLC 30/09/65 71

Aminoglycoside analysis 30/09/65 72

Aminoglycoside analysis 30/09/65 73

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Program for aminoglycosides dosing • http://www.globalrph.com/aminoglycosides .htm • Aminoglycoside Calculator - ClinCalc.com • Aminoglycoside Ca 30/09/65 86

 Develop more convenient analysis  Validated nomograms  Studies of appropriate therapeutic range in special populations  Population Pharmacokinetics 30/09/65 87

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