Aminoglycosides clearance

Aminoglycosides All NSAIDs Reduction in renal function in susceptible individuals, reducing aminoglycoside clearance and increasing plasma concentrations Careful plasma concentration monitoring and dosage adjustment... 

Studies in infants have shown that tobramycin clearance during the first postnatal week may increase with an increase in gestational age. In infants up to 1 month after birth, postnatal age also was correlated directly with aminoglycoside clearance. Thus premature infants require a lower daily dose of drugs eliminated by the kidney during the first week of fife the dosage requirement then increases with age. 

Peritoneal dialysis is less effective than hemodialysis in removing aminoglycosides. Clearance rates are -5-10 mUmin but highly variable. If a patient who requires dialysis has bacterial peritonitis, the antibiotic can be added to the dialysate to achieve concentrations equal to those desired in plasma. For intermittent dosing via peritoneal dialysate, 2 mg/kg of amikacin is added to the bag once a day. The corresponding dose for gentamicin, netilmicin, or tobramycin is... 

An aminoglycoside (consider high-concentration [once-a-day] dosing in patients with a creatinine clearance above 30 mL/min) or... 

Although most CF patients have shorter half-lives and larger volumes of distribution than non-CF patients, some patients exhibit decreased clearance. Possible causes include concomitant use of nephrotoxic medications, presence of diabetic nephropathy, history of transplantation (with immunosuppressant use and/or procedural hypoxic injury), and age-related decline in renal function in older adult patients. Additionally, CF patients are repeatedly exposed to multiple courses of IV aminoglycosides, which can result in decreased renal function. Evaluation of previous pharmacokinetic parameters and trends, along with incorporation of new health information, is key to providing appropriate dosage recommendations. 

Example. Kanamycin is a member of the aminoglycoside class of antibiotics, all of which are eliminated exclusively by glomerular filtration. Creatinine is a natural body substance that is cleared almost exclusively by glomerular filtration, and creatinine clearance rate is frequently used as a diagnostic tool to determine glomerular filtration rate. The relationship... 

Accelerated drug elimination is also a possible reason for failure and may occur in patients with cystic fibrosis or during pregnancy, when more rapid clearance or larger volumes of distribution may result in low serum concentrations, particularly for aminoglycosides. 

In fact elderly people have a reduced creatinine clearance, often balanced by the decline in creatinine input with a resulting normal serum creatinine. This is clinically important because drugs which are cleared through the kidneys need to be given in scaled down amounts to prevent cumulation and possible toxicity - e.g., gentamicin and other parenteral aminoglycosides, digoxin. 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

Zalcitabine therapy is associated with a dose-dependent peripheral neuropathy that can be treatment-limiting in 10-20% of patients but appears to be slowly reversible if treatment is stopped promptly. The potential for causing peripheral neuropathy constitutes a relative contraindication to use with other drugs that may cause neuropathy, including stavudine, didanosine, and isoniazid. Decreased renal clearance caused by amphotericin B, foscamet, and aminoglycosides may increase the risk of zalcitabine neuropathy. The other major reported toxicity is oral and esophageal... 

INDOMETACIN AMINOGLYCOSIDES T amikacin, gentamicin, and vancomycin levels in neonates Uncertain indometacin possibly 1 renal clearance of these aminoglycosides Halve the dose of antibiotic. Uncertain whether this applies to adults but suggest check levels. Otherwise use an alternative NSAID... 

Additive renal toxic effects may occur with immunosuppressants (e.g. azathioprine, ciclosporin, tacrolimus), ACE inhibitors, penicillamine, irinotecan and aminoglycoside antibiotics. A deterioration of renal function may even occur after the topical use of NSAIDs. Guidelines are variable for the use of NSAIDs with differing degrees of renal function, as assessed by creatinine clearance measurements. 

Elimination. Renal blood flow, glomerular filtration and tubular secretion decrease with age above 55 years, a decline that is not signalled by raised serum creatinine concentration because production of this metabolite is diminished by the age-associated diminution of muscle mass. Indeed, in the elderly, serum creatinine may be within the concentration range for normal young adults even when the creatinine clearance is 50 ml/min (compared to 127 ml/min in adult male). Particular risk of adverse effects arises with drugs that are eliminated mainly by the kidney and that have a small therapeutic ratio, e.g. aminoglycosides, chlorpropamide, digoxin, lithium. 

Adverse effects. Aminoglycoside toxicity is a risk when the dose administered is high or of long duration, and the risk is higher if renal clearance is inefficient (because of disease or age), other potentially nephrotoxic drugs are co-administered (e.g. 

A 72-year-old man was treated with ceftriaxone (2 g bd) and gentamicin (80 mg tds) for a severe urinary tract infection (75). On day 5 his serum potassium concentration was 3 mmol/1 with a normal serum creatinine and urine examination. Despite treatment with oral potassium chloride plus a high potassium diet, his serum potassium fell to 2.3 mmol/1 4 days later, accompanied by inappropriate kaliuresis, hypouricemia with inappropriate uri-cosuria, and hypophosphatemia with inappropriate phosphaturia. There was no bicarbonate wasting, but there was proteinuria 1.2 g/day, with a predominance of low molecular weight proteins in contrast, serum creatinine was normal and creatinine clearance was 78 ml/minute. The aminoglycoside was withdrawn with subsequent progressive improvement in renal proximal tubular function, which normalized 9 days later. 

---