1. Clinical Pharmacokinetics
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
Clinical Pharmacokinetics
PHCY 350
Lecture-7 Nomograms in Designing Dosage Regimen - Hartford Nomogram Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcome
Upon completion of this lecture the students will be able to
differentiate patient specific and physiological parameters in a population,
explain the use of nomograms in individualizing the predictions of drug dosing,
describe the use of Hartford Nomogram for dosing aminoglycosides.

3. Nomograms
Nomograms or equations, describe the relationships between patient characteristics and pharmacokinetic parameters in a population,
Used to estimate the initial pharmacokinetic parameters for drug dosing in individual patients for whom patient-specific parameters are not known.
Examples of patient characteristics are age, weight, gender, disease state (s), interacting drug (s), or environmental factor (s) (e.g., smoking and food).

4. Population data indicate that there is a significant relationship between the clearance (CL) of digoxin and the creatinine clearance (a measure of how well the kidneys function).
As creatinine clearance (CLCR) decreases, so does the clearance of digoxin.
One can actually use the reported population-based relationship for digoxin to estimate a clearance value in an individual patient based on his/her creatinine clearance.
Population-based nomograms or equations have been recommended for initial dosing of most drugs currently subjected to therapeutic drug monitoring, including aminoglycosides, digoxin, and theophylline (narrow therapeutic index).

5. In order to keep the dosage regimen calculation simple, complicated equations are often solved.
The results displayed diagrammatically on special scaled axes to produce a simple dose recommendation based on patient information.
Some nomograms make use of certain physiologic parameters, such as serum creatinine concentration, to help modify the dosage regimen according to renal function.
For many marketed drugs, the manufacturer provides tabulated general guidelines for use in establishing a dosage regimen for patients, including loading and maintenance doses.

6. Nomograms are predictive tools.
They provide individualized predictions based on the characteristics of one single patient.
The predictions are derived from hundreds or even thousands of patients who presented with the same condition.
Individualized predictions represent one of the advantages of the nomograms, relative to risk groupings of patient populations who share similar disease characteristics.

7. A nomogram typically has three scales: two scales represent known values and one scale is the scale where the result is read off.
The known scales are placed on the outside; i.e. the result scale is in the center.
Each known value of the calculation is marked on the outer scales and a line is drawn between each mark.
Where the line and the inside scale intersects is the result .
Examples include,
height – BMI – weight,
total clearance –maintenance dose – lean body weight, etc.

8. For ease of calculation of dosage regimens, many clinicians rely on nomograms to calculate the proper dosage regimen for their patients.
The use of nomogram may give a quick dosage regimen adjustment for patients with characteristics requiring adjustments such as age, body weight, and physiologic state.
In general, nomogram of a drug is based on population pharmacokinetic data collected and analyzed using a specific pharmacokinetic model.
The nomograms are meant to assist physicians with difficult clinical decision-making and to provide consistent, standardized and reliable predictions.

9. Examples of drugs for which nomograms are being used for designing dosage regimen:
Digoxin
Warfarin
Heparin
Vancomycin
Tacrolimus
Phenytoin
Clozapine
Aminoglycosides

10. Hartford Nomogram for Aminoglycosides

11. The Hartford nomogram is used for doses of 7mg/kg
The Hartford nomogram is used for doses of 7mg/kg. Obtain a single serum level 6-14 hours after the start of an infusion.
To use a nomogram, the exact time that the sample was taken in relation to the start of the infusion must be known, so it is important that this is documented on the monitoring request form.
In the example opposite, which uses the Hartford monogram, the sample was taken 10 hours after the start of the infusion.
If the serum level falls in the areas designated Q24h, Q36h or Q48h, the dose should be given every 24, 36 or 48 hours, respectively.
If the level falls on the line then the higher dosing interval should be chosen. If the level is not on the nomogram then serial levels should be obtained to determine the appropriate dosing interval