Pharmacokinetics monitoring

Inhaled tobramycin (TOBI ) is typically administered to patients 6 years of age and older in alternating 28-day cycles of 300 mg nebulized twice daily, followed by a 28-day washout or off period to minimize development of resistance. Longterm intermittent administration improves pulmonary function, decreases microbial burden, and reduces the need for hospitalization for IV therapy.24,25 Due to minimal systemic absorption, pharmacokinetic monitoring is not necessary with normal renal function. Lower doses of nebulized tobramycin solution for injection have been used in younger children, and studies are underway using 300 mg twice daily in children under age 6. 

Monitoring Monitoring serum levels is important because of the variability of chloramphenicol s pharmacokinetics. Monitor serum concentrations weekly monitor more often in patients with hepatic dysfunction, in therapy more than 2 weeks, or with potentially interacting drugs. 

The macrolide antibacterials (including erythromycin, clarithromycin and telithromycin) are often implicated in interactions, most frequently as a result of inhibition of the CYP3A4 enzyme system in the liver and enterocytes. Erythromycin inhibits the metabolism of carbamazepine, ciclosporin and theophylline significant increases in serum levels and features of toxicity have been documented. Careful clinical and pharmacokinetic monitoring are required in a patient taking any of these drugs who requires concomitant erythromycin. 

Initially, when spirorenone was tested in low doses on a male human, an unambiguous reduction of the subject s testosterone level was detected. The reason for this change was provided by pharmacokinetic monitoring, wherein it was realized that in humans and in monkeys, unlike other species, spirorenone was metabolized exclusively to 1,2-dihydrospirorenone (drospirenone), by the action of a A -hydrase (Fig. 17.5). 

Morris RG. Cyclosporin assays, metabolite crossreactivity, and pharmacokinetic monitoring. Ther Drug Monit 2000 22 160-2. 

Nahata, M.C. Intravenous infusion conditions implications for pharmacokinetic monitoring. Clin. Pharmacokinet. 1993, 24, 221-229. 

Streetman DS, Nafziger AN, Destache CJ, Bertino AS Jr. Individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity and fewer associated costs. Pharmacotherapy 2001 21(4) 443-51. 

A 17-year-old girl with a femoral osteosarcoma received her 11th cycle of methotrexate and simultaneously oral doxycycline 100 mg bd for a palpebral abscess. As in previous cycles, pharmacokinetic monitoring of methotrexate was performed. On this occasion the half-life of methotrexate was more than doubled. She developed hematological and gastroenterological toxicity. 

Bertino JS Jr, Booker LA, Franck PA, Jenkins PL, Franck KR, and Nafziger A. 1993. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring. J/nfecfD/s 167 173-179. 

Vancomycin exhibits predictable pharmacokinetic properties and its clinical use has been guided by the pharmacokinetic monitoring of serum levels to determine the dose and frequency of administration. Pharmacokinetic monitoring of vancomycin, however, has become increasingly controversial given the improved safety of this antibiotic and the lack of data to support what are considered the therapeutic and toxic serum levels. Historically, the most severe toxicities of vancomycin were ototoxicity and nephrotoxicity. The incidence of nephrotoxicity has declined since its introduction possibly due to the availability of purer forms of the antibiotic. Ototoxicity has always been a rare adverse event of vancomycin, but it has been observed with excessively high concentrations of the drug in plasma [170-172]. The purpose of this section is to describe the nephrotoxicity associated with the clinical use of vancomycin. 

Buchowsky SS, Partovi N, Ensom NH. 2005. Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 27 322-333. 

Drug utilization review Pharmacokinetic monitoring Drug formulary management Pain management Drug research and studies Nutrition... 

ASHP Statement A declaration and explanation of basic philosophy or principle, as approved by the Board of Directors and the House of Delegates. ASHP Statements cover such topics as the pharmacist s role in clinical pharmacokinetic monitoring, infection control, and primary care. 

Initially, many pharmacokinetics services were centralized programs with only specialists in pharmacokinetics providing these services.The more recent advent of pharmaceutical care, however, has led to more integrated approaches such that clinical pharmacokinetic monitoring is becoming a fundamental responsibility of... 

At the University of Kentucky Medical Center, the primary pharmacist or pharmacy resident who attends rounds or precepts pharmacy students on a primary medical team is responsible for clinical pharmacokinetic monitoring of all patients on that team. The Clinical Pharmacokinetics Service oversees the pharmacokinetic monitoring process for all patients [i.e., those on teams with assigned pharmacists ( covered )], as well as those who are on teams that do not have an assigned primary pharmacist or resident ( noncovered ). The Clinical Pharmacokinetics Service consists of a faculty member who serves as the director and of pharmacy practice residents and senior pharmacy students during their clinical pharmacokinetic rotations. ... 

Numerous studies on clinical pharmacokinetic monitoring have demonstrated positive clinical outcomes. The reader is directed to a comprehensive review of the evidence to support such definitive outcomes.Some examples of positive clinical outcomes for theophylline monitoring cited in the comprehensive review include decreased length of stay and decreased toxicity. For traditional aminoglycoside monitoring, examples include decreased length of treatment,decreased length of hospital stay, ° " decreased febrile periods decreased duration to return to normal or baseline temperature, decreased duration to stabilize heart... 

Several of these studies evaluating the impact of clinical pharmacokinetic monitoring on patient outwore also cited in a 1996 landmark... 

Pharmacokinetic monitoring of cancer patients on methotrexate has been found to significantly reduce the incidence of serious toxicity and virtually eliminate death due to high-dose methotrexate. " Other examples for other drugs are discussed in a state-of-the-art paper on pharmacokinetic optimization of cancer chemotherapy and its effect on outcomes. " ... 

American Society of Health-System Pharmacists Statement on the Pharmacist s Role in Clinical Pharmacokinetic Monitoring This is a position statement that provides background information and lists responsibilities that should be a part of clinical pharmacokinetics services or monitoring conducted by all pharmacists. In addition, a list of responsibilities that should be assumed by pharmacists with specialized education, training, or experience in pharmacokinetics is provided. ... 

Horn, J.R. Christensen, D.B. deBlaquire, P.A. Evaluation of a digoxin pharmacokinetic monitoring service in a community hospital. Drug Intell. Clin. Pharm. 1985, 19, 45 52. 

The pharmacist provides pharmacokinetic monitoring when a targeted drug is prescribed. 

The pharmacist documents clinical activities that include, but are not limited to, disease state management, general pharmacotherapeutic monitoring, pharmacokinetic monitoring, ADEs, education, and other patient care activities. 

University-affiliated community hospital Pharmacokinetic monitoring To determine cost benefit of pharmacokinetic services for patients receiving aminoglycosides 75.84 1 and 52.25 1... 

University hospital Pharmacokinetic monitoring To evaluate impact of computer-assisted aminoglycoside dosing 4.09 1... 

To evaluate OD impact of clinical RPh on cost and quality of patient care Pharmacokinetic monitoring service None None Physician acceptance, patient outcome indicators, DCA 205 interventions made during 6-mo study 80.9% made to increase quality 18.1% to increase quality and decrease cost ... 

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