Pharmacokinetics therapy

Engineering Aspects of Hemodialysis. Engineering interest in hemodialysis is concentrated on the optimization of the hemodialysis membrane (4,41), the dependency of solute removal on membrane and device characteristics (14,15), and quantitation of hemodialysis therapy through urea pharmacokinetics (42—44). 

Urea Pharmacokinetics. Pharmacokinetics summarizes the relationships between solute generation, solute removal, and concentration in a patient s blood stream. In the context of hemodialysis, this analysis is most readily appHed to urea, which has, as a consequence, become a surrogate for other uremic toxins in the quantitation of therapy and in attempts to describe its adequacy. In the simplest case, a patient is assumed to have no residual renal function. Urea is generated from the breakdown of dietary protein, accumulates in a single pool equivalent to the patient s fluid volume, and is removed uniformly from that pool during hemodialysis. A mass balance around the patient yields the following differential equation ... 

Design of a controUed release dosage form requires sufficient knowledge of both the desired therapy to specify a target plasma level and the pharmacokinetics. The desired dmg input rate from a zero order system may be calculated by ... 

Patients receiving cytotoxic chemotherapy very often need concomitant administrating of antiemetic therapy. Such protocols will start well in advance of administering the cytotoxic, and last for a reasonable time with regard to pharmacokinetics of the antineoplastic agent. In addition, side effects of antineoplastic therapy are made better tolerable by supportive care. 

Drug-drug interactions Pharmacokinetic and/or pharmacodynamic interactions Pharmacokinetic and/or pharmacodynamic consequence of multiple drug therapy... 

In clinical life, as outlined in this essay, pharmacokinetics (PK) is used instrumental to improve drug therapy. For this purpose, pharmacokinetics must be presented in general and transmissible terms. The case of kidney failure gives one important example of how disease influences pharmacokinetics and how pharma-cokonetics can be used to produce the same pharmacodynamic effect is such patients. The aim and end... 

King JR, Wynn H, Brundage R, Acosta EP (2004) Pharmacokinetic enhancement of protease inhibitor therapy, Clin Pharmacokinet 43 291-310... 

The requirements of protease inhibitors as drugs in terms of potency, pharmacokinetics, and toxicity will vary depending on the nature of the infection and the goals of therapy. At one extreme is treatment of HlV-1, a chroific infection that requires life-long therapy and full suppression of viral replication. At the other extreme is the treatment of human rhinovirus (i.e., the cold virus), where short-term treatment to blunt viremia will likely be sufficient to reduce the unwanted symptoms of a cold. In all cases, viral proteases represent very attractive targets with familiar mechanisms of catalysis that frequently allow for the design of transition state analogs and with distinct specificities from host proteases. 

David Taylor is Chief Pharmacist at the South London and Maudsley NHS Trust. Honorary Senior Lecturer at the Institute of Psychiatry and Foundation President of the College of Mental Health Pharmacists. His main areas of research are pharmacokinetics and prescribing practice in mental health. His team at the Maudsley is widely involved in systemic reviews and meta-analyses of psychotropic drug therapy. David is lead author of the Maudsley 2001 Prescribing Guidelines (Martin Dunitz, 2001) and co-editor of Case Studies in Psychopharmacology (Martin Dunitz, 1998). 

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. 

Although EPO deficiency is the primary cause of CKD anemia, iron deficiency is often present, and it is essential to assess and monitor the CKD patient s iron status (NKF-K/DOQI guidelines). Iron stores in patients with CKD should be maintained so that transferrin saturation (TSAT) is greater than 20% and serum ferritin is greater than 100 ng/mL (100 mcg/L or 225 pmol/L). If iron stores are not maintained appropriately, epoetin or darbepoetin will not be effective, and most CKD patients will require iron supplementation. Oral iron therapy can be used, but it is often ineffective, particularly in CKD patients on dialysis. Therefore, intravenous iron therapy is used extensively in these patients. Details of the pharmacology, pharmacokinetics, adverse effects, interactions, dose, and administration of erythropoietin and iron products have been discussed previously. 

Therapeutic drug monitoring (TDM) or applied pharmacokinetics is the use of serum drug concentrations to optimize therapy.28,36,37 Non-AIDS patients with drug-susceptible TB... 

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

The pharmacokinetics of bevacizumab demonstrate a terminal half-life of 21 days, with a volume of distribution consistent with limited extravascular distribution.34 Bevacizumab has shown clinical activity in the treatment of colorectal, kidney, lung, breast, and head and neck cancer. Patients may develop hypertension requiring chronic medication during therapy. Impaired wound healing, thrombolembolic events, proteinuria, bleeding, and perforation are serious side effects. 

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