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Appropriateness of a 4 mg/kg gentamicin or tobramycin loading dose in post‐operative septic shock patients
Author(s) -
Oparaoji E. C.,
Siram S.,
Shoheiber O.,
Cornwell III E. E.,
Mezghebe H. M.
Publication year - 1998
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1046/j.1365-2710.1998.00126.x
Subject(s) - tobramycin , septic shock , loading dose , pharmacokinetics , medicine , gentamicin , liter , aminoglycoside , volume of distribution , anesthesia , regimen , dosing , shock (circulatory) , surgery , antibiotics , chemistry , sepsis , biochemistry
Objective:To determine the frequency with which early adequate peak serum concentrations (6–12 mg/litre) can be achieved following a 4 mg/kg loading dose of gentamicin or tobramycin in post‐operative septic shock patients. Method: Eleven post‐operative septic shock patients were grouped into (i) a control group (n=7) who received the conventionl gentamicin or tobramycin dosing regimen of 2 mg/kg loading dose followed by a maintenance dose of approximately 1·5 mg/kg (peak and trough levels were measured after the third dose), and (ii) a study group (n=4) who received a tobramycin or gentamicin 4 mg/kg loading dose, followed by 30 min, 3 h and 16 h serum drug level measurements. Pharmacokinetic parameters were calculated using a one‐compartmental model. Differences in both groups were determined using Student's t ‐test. Results: Pharmacokinetic parameters in both groups showed no statistically significant difference. The dose from which peak levels were drawn was significantly higher in the study group (4 mg/kg vs. 1·66 mg/kg; P=0·001), which also resulted in higher but adequate peak serum concentrations (8·9±2·2 vs. 4·8±1·8 mg/litre). In the study group, linear regression analysis showed significant relationships between dose and peak concentrations and volume of distribution and peak concentrations (r =0·96, P =0·01 and r=−0·96, P =0·01, respectively). Conclusion: One hundred per cent of the post‐operative septic shock patients achieved target peak serum concentrations (mean 8·9±2·2 mg/litre) following a 4 mg/kg tobramycin or gentamicin loading dose. An expanded V d (0·46±0·13 litres/kg) was also observed.