MEDICINE
Systematic Clearance Extended Calculation
Fraction Unbound (fu): 0.5
Clearance by active Secretion (CLsec):5.4/Lhr
Fraction reabsorbed (FR): 0.2
Hepatic Extraction Ratio (Eh): 0.1
Calculating the (Vd): Volume of Distribution of drug on administration =Vd=Xo/Co
Vd= Xo/Co =300mg/Anti-log1.26
Vd = Xo/Co = 300mg/18.2 ug/ml = 16.5lts
Total Systematic Clearance, ClT = ClT=KeVd
ClT = KeVd = 5.4/hr x 16.5 lts =0.299/60mins x 1000ml
= (4933.5/60)ml/min = 82.23ml/min
Assumptions:
i) The Dose was administered intravenously
ii) Co= Drug Plasma Concentration at zero time after it was administered
Therapeutic monitoring
Population pharmacokinetics is the study that focuses on the mean and the variability in the pharmacokinetic procedures and model perimeters of a drug within a specialized population .There are factors that cause variability in drug response .There are six major factors of variability in drug response. These are body weight, genetics, disease, concurrent drugs and non-adherence to medication. The patient population treated and the responses determine the significance of each drug. Amongst the major factor, listed genetics is the most complex and not easy to comprehend (Wilkinson, 2005 p.252). However, with improved technology in the medical field avenues have been created to forecast outcome from genomic data.
A circumstance and population where variability may be most important is during the clinical development of medicine used by children. Limited information is on this variability is generated through, medical trials. The guidelines set aim to monitor medication safety in the pediatric field.
There are several methods used to control variability in ensuring the safety of medicine. One of the approaches is pharmacovigilance, which is a scientific method that ensures the detection, assessment, perceptive and prevention of adverse effects or any problems related to medicine. This approach does not only view the reactions during the regular use of a particular medicine but also reactions due to errors in non-adherence, administration, drug abuse and off-label use. Without pharmacovigilance especially in underdeveloped countries, children and adolescents face many risks such as counterfeit medicine and over the counter non-medical prescription for teenagers. Sometimes adults with little buying power find it cheap to borrow medicine from relatives or neighbors.
Intra-individual Variability
Small therapeutic index drugs, for which the therapeutic dose is close to the dose giving undue adverse events, have a low intra-individual variability in both pharmacokinetics and pharmacodynamics (Eriksson, 2003 p.35). Genetic factors contribute to the intra-individual variability of new cancer drugs. Studies have shown that different forms of cancer are diverse in etiology and are of heterogeneous composition, this explains why cancer is difficult to treat. The heterogeneity nature of the disease affects the modes of action of drug.
However, there are different genetic effects on drug pharmacokinetics, once the cancer is the body system it encounters various molecular components as it transits through the body to where the tumor is located. During the initial stages of the drug’s presence in the body, the drug’s pharmacokinetics is affected and therefore a change in the amount of drug that reaches the tumor (Maeda.H, 2001 p189). Other effects include the papulo-pustular skin, which is a rash that appears on the skin because of genetic drug intake. Most cancer patients though prefer oral medication to other developed methods such as chemotherapy because they include fewer hospital visits, venipunctures and side effects. Toxicity levels in the new anti-cancer are relatively lower as compared to those of the traditional chemotherapeutic and are less focused on the blood cells.
References
Eriksson, U. G., Bredberg, U., Gislén, K., Johansson, L. C., Frison, L., Ahnoff, M., & Gustafsson, D. (2003). Pharmacokinetics and pharmacodynamics of ximelagatran, a novel oral direct thrombin inhibitor, in young healthy male subjects. European journal of clinical pharmacology, 59(1), 35-43.
Maeda, H. (2001). The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Advances in enzyme regulation, 41(1), 189-207.
Wilkinson, G. R. (2005). Drug metabolism and variability among patients in drug response. New England Journal of Medicine, 352(21), 2211-2221.
