Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 56

Because the kidney represents one of the major routes of drug elimination, a decline in renal function can influence the clearance of many drugs. If a drug normally cleared by the kidney is given to someone with decreased renal function without altering the dose, the steady‐state blood concentrations of that drug will be increased. This is of considerable importance in the case of drugs showing concentration‐related effects, particularly those that have a narrow therapeutic range.

When such drugs are given to patients with renal dysfunction, the general aim is to achieve similar concentrations to those seen in patients with normal kidneys.

Therapeutic concentrations can be maintained by:

1 Determining renal function, usually by estimating creatinine clearance

2 Modifying the dose using a nomogram, either by increasing the dosage interval, or by giving a lower dose at the same interval or by altering both the dose and the interval. The extent and precision of dose modification depend very much on the toxicity of the drug concerned. In the case of the aminoglycosides, even minor impairment of renal function requires some dosage alteration, while the dose of penicillins need only be reduced in severe renal failure (creatinine clearance <10 mL/min). Guidance on dosage modification is readily available for most commonly used drugs. It should be noted that the loading dose is usually not changed by renal impairment because this depends more on the volume of distribution of the drug than its rate of elimination

3 Monitoring drug concentrations. This is useful for drugs with concentration‐related adverse effects, such as the aminoglycosides, digoxin, aminophylline, phenytoin and carbamazepine, and mandatory for lithium, ciclosporin (cyclosporin) and methotrexate. Nomograms are useful guides to the doses likely to be appropriate, but every patient is different. Concentrations of drugs in the blood can be used to assess clearance and to determine the most appropriate dose for individual patients