**14.11. Maintenance dose**

In most clinical situations drugs are administered in such a way as to maintain a steady concentration i.e. just enough drug is given in each dose to replace the drug eliminated since the preceding dose. Therefore, clearance is the most important pharmacokinetic term to be considered in defining a rational steady-state drug dosage regimen.

Clearance should also be adjusted for the size of the patient and for convenience, the published

Introduction to Biochemical Pharmacology and Drug Discovery

http://dx.doi.org/10.5772/52014

509

When clearance is low, t1/2 is similarly high and when the volume of distribution is high, the t1/2 is also high. Therefore, by using parameters for the individual patient, the dosing rate = Tc x Cl/F where, Tc = target concentration, Cl = clearance and F = fractional availa‐

If a drug is relatively non toxic then the maximum loading strategy can be employed so that the dosing interval is much longer than t1/2.. For example t½, of penicillin is less than one hour but it is usually given in very large doses every six to twelve hours since it is non-toxic. The normal steady-state theophylline concentration can be determined using the equation:

Where, Css, max and Css min are the maximum and minimum steady state concentrations,

Drug absorption in the elderly is slightly different from the normal patients and therefore adjustment of the dosage should be taken into consideration during drug therapy. The rate of transdermal drug absorption may be diminished in elderly because of reduced tissue blood perfusion. Compounds that permeate the intestinal epithelium by carrier mediated transport

In geriatrics the 'body mass' declines with age and the total body water content falls by between 10 – 15%. The volume of distribution of hydrophilic drugs will therefore decrease while plasma concentration will increase and the likelihood of toxic drug effects will also increase. When geriatric patients use diuretics, the extracellular space reduces even further leading to a higher likelihood of drug toxicity. The total body fat in the elderly increases by 12 – 18%, therefore, for hydrophobic drugs, the higher volume of distribution implies an increase in half life of distribution and the time needed to reach steady-state serum concentration. Therefore, for geriatrics a once or twice daily drug administration is optimal. This can be achieved though

Drug treatment of any kind is often compromised by lack of full compliance by the patient. The common errors of compliance to a regimen by a patient include; omission in taking the

values are normalized to the metabolic rate = weight 0.75.

bility of the drug.

F.dose/Vss 1 – exp(-KT)

T = dosage interval and K = 0.693

**14.14. Drug distribution**

F.dose/Vss. (exp-KT) 1 – exp(-KT)

t½

**14.13. Drug dosage adjustment in old patients (geriatrics)**

mechanisms may be absorbed at lower rates in the elderly.

delayed release or fixed drug combinations.

**14.15. Patient compliance and rational use of drugs**

Css, max =

Css, min =

The rate of elimination = Cl x Tc

Where, Cl is the rate of clearance and Tc is the target concentration of the drug.

The Dosing rate = Rate of elimination = Cl x Tc.

Therefore, if the target concentration is known, the prevailing clearance in that patient will determine the dosing rate and if the drug is given by a route that has a bio availability of less than 100%, then the dosing rate above can be modified using the formula:

Dosing rate oral = Dosing rate Fractional availability

If intermitted doses are given, then maintenance dose = Dosing rate x Dosing interval.

#### **14.12. Alteration of maintenance dose**

The maintenance dose is usually altered when the clearance of the drug changes. For example, during renal impairment, the clearance of drugs which are predominantly cleared by the kidney is greatly reduced and therefore, the desired steady state concentration can only be achieved either through altering the dose or altering the dosing interval. Therefore, when a drug is cleared almost completely via kidneys, the dosage interval should be changed in proportion to renal clearance as follows:

The % eliminated in dosing interval should be proportional to creatinine clearance by a published constant to yield the percentage excreted in one dosage interval.

The quantities required for this adjustment are:


The fraction of normal function remaining is equal to the ratio of patient's creatinine clearance to a normal value (120 ml/min/70kg).

The following equation is for adjustment of renal clearance

$$\text{rf}\_{\text{pt}} = 1 - \text{fe}\_{\text{nl}}(1 - \text{rfx}\_{\text{pt}})$$

Where;

rfpt = the adjusted total clearance of the patient,

fenl = fraction of drug excreted unchanged in normal individuals,

rfxpt = fraction of renal clearance of the normal individual.

Clearance should also be adjusted for the size of the patient and for convenience, the published values are normalized to the metabolic rate = weight 0.75.

When clearance is low, t1/2 is similarly high and when the volume of distribution is high, the t1/2 is also high. Therefore, by using parameters for the individual patient, the dosing rate = Tc x Cl/F where, Tc = target concentration, Cl = clearance and F = fractional availa‐ bility of the drug.

If a drug is relatively non toxic then the maximum loading strategy can be employed so that the dosing interval is much longer than t1/2.. For example t½, of penicillin is less than one hour but it is usually given in very large doses every six to twelve hours since it is non-toxic. The normal steady-state theophylline concentration can be determined using the equation:

$$\text{Css, max} = \frac{\text{F.dose/V}\_{\text{ss}}}{1 - \exp^{\text{(-KT)}}}$$

$$\text{Css, min} = \frac{\text{F.dose/V}\_{\text{ss}} \cdot \text{(exp}^{\text{-KT}}\text{)}}{1 - \exp^{\text{(-KT)}}}$$

**14.11. Maintenance dose**

508 Drug Discovery

The rate of elimination = Cl x Tc

Dosing rate oral = Dosing rate

**14.12. Alteration of maintenance dose**

proportion to renal clearance as follows:

to a normal value (120 ml/min/70kg).

rfpt= 1 – fenl(1 – rfxpt)

Where;

The quantities required for this adjustment are:

rfpt = the adjusted total clearance of the patient,

**i.** Fraction of normal function remaining, and the

**ii.** Fraction of drug usually excreted unchanged in urine.

The following equation is for adjustment of renal clearance

fenl = fraction of drug excreted unchanged in normal individuals,

rfxpt = fraction of renal clearance of the normal individual.

The Dosing rate = Rate of elimination = Cl x Tc.

Fractional availability

In most clinical situations drugs are administered in such a way as to maintain a steady concentration i.e. just enough drug is given in each dose to replace the drug eliminated since the preceding dose. Therefore, clearance is the most important pharmacokinetic term to be

Therefore, if the target concentration is known, the prevailing clearance in that patient will determine the dosing rate and if the drug is given by a route that has a bio availability of less

The maintenance dose is usually altered when the clearance of the drug changes. For example, during renal impairment, the clearance of drugs which are predominantly cleared by the kidney is greatly reduced and therefore, the desired steady state concentration can only be achieved either through altering the dose or altering the dosing interval. Therefore, when a drug is cleared almost completely via kidneys, the dosage interval should be changed in

The % eliminated in dosing interval should be proportional to creatinine clearance by a

The fraction of normal function remaining is equal to the ratio of patient's creatinine clearance

If intermitted doses are given, then maintenance dose = Dosing rate x Dosing interval.

considered in defining a rational steady-state drug dosage regimen.

Where, Cl is the rate of clearance and Tc is the target concentration of the drug.

than 100%, then the dosing rate above can be modified using the formula:

published constant to yield the percentage excreted in one dosage interval.

Where, Css, max and Css min are the maximum and minimum steady state concentrations,

T = dosage interval and K = 0.693 t½
