**a. Define Cpmin/Cpmax.** From information on the drug with reference to
the patient's clinical requirements. For example the normal upper limit for
gentamicin peak concentrations might be 6 mg/L, however in case of life-threatening
infection higher levels may be approached. Initial calculation might be based
on a peak of 6 mg/L and a trough below 1 mg/L. (Use 1 mg/L as the trough and
extend the interval when making the adjustment in .

**b. Determine CLcr.** Probably from serum creatinine levels using the
Cockcroft-Gault equation.

**c. Determine kel.** Using the equation kel = km + b * CLCr with km and b
values from the literature

**d. Calculate Tau.** Since
and we know Cpmin, Cpmax, and kel we can calculate tau, . Typically this
will be some uneven time value.

**e. Round Tau.** A more usual dosing interval should now be chosen. For
example a tau of 7.8 or 6.7 hour could be rounded to 8 hours, thus dosing three
times a day.

**f. Recalculate R.** A new value of tau results in a new value of R.

**g. Calculate Maintenance Dose.** The maintenance dose can be calculated
from the minimum or the maximum plasma concentration. Thus

Maintenance dose = Cpmax * V * (1 - R) **OR**
= Cpmin * V * (1 - R)/R

**h. Calculate Loading DOSE.** The loading dose can be calculated directly
(for an iv bolus) by equating Cp^{0} and the Cpmax value. Thus,

Loading dose = Cpmax * V

**Example:**

A 75 kg, 65 year old male patient, serum creatinine concentration of 2.3 mg/100
ml, is to be given gentamicin iv to achieve a peak plasma concentration of 6
mg/L and trough concentration **below** 1 mg/L. The apparent volume of
distribution is reported to be 0.28 L/kg[4].
From table 16-3
(Niazi), km and b values are 0.02 and 0.0028, respectively.

a. Cpmax = 6 mg/L and Cpmin = 1 mg/L

b. CLcr =

c. kel = km + b * CLcr = 0.02 + 0.0028 x 34 = 0.115 hr^{-1}

d. R =

ln (0.1667) = -1.792 = -0.115 x

= 15.6 hour

e. Since a longer dosing interval is needed to keep the trough level
**below** 1 mg/L use a tau value of 18 hours.

f. New R value. R = e^{-0.115 x 18} = 0.1262

g. Calculate maintenance dose using Cpmax = 6 mg/L as reference point. Thus

Maintenance dose = Cpmax * V * (1 - R) = 6 x 75 x 0.28 x (1 - 0.1262) = 110 mg

Thus use 100 mg iv every 18 hours

Cpmin = Cpmax * R = 5.45 x 0.1262 = 0.69 mg/L

h. The loading dose can be calculated as:-

Loading dose = Cpmax * V = 6 x 75 x 0.28 = 126 mg. Using 125 mg would give a Cpmax = = 5.95 mg/L.

Thus a loading dose of 125 mg followed by 100 mg every 18 hours should be satisfactory.

Comparison with PDR recommendation.

Usual dose for 75 kg patient is 75 mg q8h. With serum creatinine 2.3 mg/100 ml give 40 percent of 75 mg q8h. That is 30 mg q8h (R = 0.399) giving 2.38 and 0.95 for Cpmax and Cpmin, respectively.

This page was last modified: 13 October 2001

Copyright 2001 David W.A. Bourne