There was no dropout of any patient during the study. Serum concentrations of amikacin in 6 patients following intravenous infusion over a period of 30 minutes of drug and pharmacokinetic parameter based on this data has been shown in table 1
and graphically in figure 1
Use of 6 patients is insufficient and any differences from previous studies are difficult to interpret. Such limitations usually encounter during studies in target patients. However, such studies would be of empiric value.
According to the MAIC values implemented in PK II, amikacin serum concentration-time data in all patients fitted to a two compartment open model. In a preceding study, the pharmacokinetic of amikacin assumed one-compartment model in neonates with bacterial infection . However, as reported by Maller et al  a bi-compartmental approach is appropriate for describing pharmacokinetics of amikacin since triexponential equation is inapplicable due to undetectability of a slow terminal elimination phase in serum drug-concentration profile. On the other hand, a uni-exponential equation leads to erratic conclusions about the elimination rate of amikacin.
The exact reasoning of this variation cannot be presented. However, this may be attributed to fluctuations in volume of distribution (Vd) and modifications in the physiological and biochemical parameters under influence of disease. Use of different computational approaches for the calculation of amikacin pharmacokinetics can be added as a source of this variation.
Mean serum concentration of amikacin following short-term infusion in 6 pediatric patients in this study was measured as 36.30±4.03 mg/ml. The normal cited values of serum concentration of amikacin are 19 to 43.8 mg/l in children . The present value of amikacin concentration is in the same order of magnitude of 43.7±13.8 and 31.46 mg/ml observed in neutropenic and in cystic fibrosis pediatric patients, respectively [13,14]. However, this value varied widely from 21 mg/ml in hematologic malignant patients .
These differences may be attributed to diseased condition and various patient factors (PFs). Reports suggest that the PFs, like renal function, fever, hematocrit value, lean body weight and age are related to amikacin elimination and thereby influence serum concentration .
Area Under Serum Concentration-Time Curve and Mean Residence Time (MRT)
The area under the curve (AUC0-¥) of amikacin in present study was observed to be 76.20±6.30 ìg.hr/ml. Drug AUMC0-¥ was observed to be 190.26±31.61 mg.hr2/ml. Amikacin dose, as indicated by value of mean residence time (MRT), persisted in body for a period of 2.15±0.62 hours. The values of MRT in normal and diseased conditions have not been cited in children; however, in normal adults it is 2.76 hours .
The distribution half life (t1/2a) of amikacin was concluded to be 0.04±0.02 hrs. The value of these parameters has not been cited in any of the preceding study.
The present value for t1/2elim (1.76±0.55 hrs) is in agreement with the reported usual range of 0.68-2.10 hrs in children and 1.45 hrs in febrile neutropenic pediatric patients [12,14,17,18]. However, this value is less than 3.0 and 3.8±2.4 hrs in patients with hematologic malignancies [5,6]. The t1/2elim in pediatric population is reported to be briefer than those in diseased adult population on accounts of a larger Vd and a faster clearance in infants and children [19,20].
Wide variations were observed particularly for body clearance (Cl) when its values (18.85±5.11 ml/min) were compared with the cited values in normal as well as in diseased populations. The normal reported value for this parameter is 155 ml/min/1.73 m2±17.4 in children . The amikacin is primarily eliminated by glomerular filtration and thus modifications in renal function should directly affect the drug’s clearance. A large amount of variance in clearance of drug has also been explained by modifications in creatinine clearance . The Cl is also reported to be increased in cancer patients .
Volume of Distribution
The current value of volume of distribution (Vd) of amikacin was observed to be 0.19±0.11 l/kg. The normal values for this parameter have been mentioned as 0.27±0.04 l/kg in children . From other reports, the value of Vd has been varied from 0.38 and 0.41 l/kg in cancer patients [3,5,6].
Aminoglycoside antibiotics distribute to a volume similar to the extracellular fluid compartment [22,23]. The Vd of amikacin is reported to be markedly elevated in hematologic malignancies compared with normal [3-5]. This has been attributed to substantial changes in extracellular fluid compartment in patients with severe sepsis as a result of changes in state of hydration [23,24]. Davis and coworkers  attributed this increased Vd due to lower serum albumin concentrations by an unknown mechanism. But, according to them, it may be due to low venous oncotic pressure that results in increased extracellular fluid. Since aminoglycosides are distributed readily to that space, the Vd would be increased in sepsis-induced hypoalbumineamia.
The Vd of amikacin is reported to have a substantial effect on its peak serum concentration and consequently, the dosage requirements of amikacin [24,25]. In patients with contracted volume, lower dosages while for that with expanded volumes, larger dosages of amikacin are needed to achieve desired peak levels . Increase in Vd and Cl causes a sub-therapeutic serum amikacin concentration if dosage adjustment of the drug is not made . In our study, both parameters are seemed to be descended as compared to normal reported values, however, more data and studies are needed to confirm these results.
Table 1: Mean±SD serum concentration and pharmacokinetic parameters of amikacin after i.v. infusion of the drug in 6 cancer patients
Figure 1: Mean±SD serum amikacin concentration in six cancer patients after i.v. infusion