In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic. In this study we report on a 6-year follow-up audit since our first assessment of the service.
This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs. A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed. We review the lack of standardization of definitions for aminoglycoside-associated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed. The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.
In a prospective study on 47 patients, 16 mg of gentamicin per two litres dialysate was administered intraperitoneally at every cycle of intermittent peritoneal dialysis, carried out over the course of several days. Serum gentamicin sampling, pure tone audiometry and caloric tests were performed before and during the treatment. The gentamicin levels reached at the end of the thirtieth cycle were observed to be low. In view of this, the risk of acute ototoxicity was considered to be minimal. This was confirmed by the absence of clinical audiometric or vestibulometric evidence of toxicity.
A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.
To determine the ameliorative potential of the active fraction from different extracts of Rumex vesicarius against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats and its possible mechanism of action. Both sex wistar rats were divided into 6 groups (n=6/group) were fed with a control, potassium dichromate and gentamicin supplemented with different extracts at the doses of 200 and 400mg/kg respectively. Oral administration of EERV offered a significant (p<0.01 and p<0.001) dose dependent protection against PD and GN induced nephrotoxicity. Potassium dichromate and gentamicin nephrotoxicity assessed in terms of body weight, kidney weight, creatinine, urea, uric acid, BUN, albumin and total protein. Thus the present study revealed that EERV phytochemical constituents play an important role in protection against kidney damage.