No abstract available.

No abstract available.

The third equation on page 44 should be corrected.

The equations on page 162 should be corrected.

In the published version of this article, the contents of Table 1 (‘Demographic characteristics of subjects’) are incorrect.

Drug-drug interaction (DDI) is defined as a change in effect or safety of a drug by another co-administered drug. The fact that more than half of the market withdrawal cases for the past ten years was caused by potentially fatal DDI's demonstrates its clinical importance. The mechanism of DDI can be categorized into pharmacokinetic and pharmacodynamic interactions. Most of the clinically important drug interactions are caused by inhibition or induction of oxidative metabolism by cytochrome P450 (CYP) isozymes. Recent researches are also focusing on drug transporter interactions as another significant factor underlying DDI's. It is hard to prevent unexpected or rare DDI's. However, most of the cases of DDI occur from an erroneous prescription of drugs that are already known to result in deleterious interactions. To avoid such well-established DDI's, physicians are first recommended to utilize hands-on summary tables for CYP substrates before prescribing. It should also be remembered that old age, polypharmacy and damaged hepatic or renal function are risk factors of DDI as well as adverse drug reactions. Moreover, patients treated with drugs with a narrow therapeutic index (immunosuppressants, antiarrhythmics, anticoagulants, digoxin, theophylline etc) deserve a special consideration when their prescriptions are changed. In Korea, the clinical significance of DDI has been underemphasized. The fundamental prescription to this old prescription habit is to teach medical students and physicians clinical pharmacology and therapeutics, which have long been neglected in Korea.
Anticoagulants ; Cytochrome P-450 Enzyme System ; Digoxin ; Drug Interactions ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Isoenzymes ; Korea ; Metabolism ; Pharmacology, Clinical ; Polypharmacy ; Prescriptions ; Product Recalls and Withdrawals ; Risk Factors ; Students, Medical ; Theophylline

This tutorial deals with basic concepts of clearance, the most important parameter in pharmacokinetics but often challenging for students in clinical pharmacology. Its relationships with dose, concentration and elimination rate are discussed using a physical model and examples of commonly used drugs, as well as its physiological aspects pertaining to the blood flow to differing organs. Finally, application of clearance to the calculation of maintenance dose rate and half-life is used to show how it is essential in pharmacotherapy and clinical pharmacology.
Drug Therapy ; Half-Life ; Humans ; Pharmacokinetics ; Pharmacology, Clinical

To address the debate on the safety of generic substitution quantitatively, the author compared the change in AUC in virtual patients who were simulated for several different scenarios of generic substitution. In four scenarios of original (branded) to generic and generic to generic substitution, 5,000 virtual patients were simulated per scenario using the programming software R. The mean population AUC of generics ranged from 90-110% (scenarios A and B) and 80-123.5% (scenarios C and D) of the AUC of the original. Those patients who had an AUC change (ratio) as a result of drug substitution of less than 0.67 or greater than 1.5 were considered to be in potential danger due to the substitution. We found that less than 6% of patients fell outside of the cutoff range of 0.67-1.5 as a result of original to generic substitution. However, in the case of generic to generic substitution, the proportion was as high as 9-12%. This alerts us to the potential danger of generic substitution, especially for drugs with narrow therapeutic indices.
*Area Under Curve ; Attitude to Health ; Computer Simulation ; Drug Prescriptions ; Drugs, Generic/*pharmacokinetics/therapeutic use ; Humans ; Patients/psychology/statistics & numerical data ; Software ; Therapeutic Equivalency

Therapeutic plasma exchange is used in almost every condition in which there is a plasma factor thought possibly to the etiology or pathogenesis of a disease or one of its manifestations. In order to evaluate plasma exchange using fresh frozen plasma as replacement solution, eighty four therapeutic plasma exchanges were carried out in eighteen patients. In standardized procedures, 1.5 times the calculated plasma volume was replaced with a Hartman's solution and fresh frozen plasma. Anticoagulation was achieved using a whole venous blood to 2.5% trisodium citrate in the ratio of 10 to 1. Total calcium, phosphorus, glucose, urea nitrogen, creatinine, bilirubin, alkaline phosphatase, amylase, creatine kinase, IgG, C3, total white and red blood cell count, hemoglobin, and differential count were not significantly affected by the procedure. In contrast, serum cholesterol, total protein, albumin, aspartate aminotransferase, alanine aminotransferase, ionized calcium, IgM, C4 and platelet were significantly decreased by the plasma exchange. All these measurements had returned to the first pre-exchange level within 24 hours, while the C4 and platelet count took between 24 and 72 hours, and the IgM level, between 72 hours and 1 week. These data indicated that in an isovolemic plasma exchange there was a transient but rapidly reversible effect on all the components studied, with C4 and platelet count, returning more slowly to pre-exchange level than the others, and IgM levels responding the slowest. In summary, plasma exchanges using fresh frozen plasma as replacement solution were assumed to be not significantly affected the function of various organs.
Alanine Transaminase ; Alkaline Phosphatase ; Amylases ; Aspartate Aminotransferases ; Bilirubin ; Blood Platelets ; Calcium ; Cholesterol ; Citric Acid ; Creatine Kinase ; Creatinine ; Erythrocyte Count ; Glucose ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Nitrogen ; Phosphorus ; Plasma Exchange* ; Plasma Volume ; Plasma* ; Platelet Count ; Urea

More than 60 antiviral agents for various infectious diseases such as herpes, hepatitis, influenza, and AIDS are currently prescribed worldwide. Among the viral infections, hepatitis B and influenza are those frequently seen in primary care situations in Korea. This review discusses the anti-hepatitis B (HBV) drugs entecavir and adefovir, and the anti-influenza drugs oseltamivir and zanamivir. In addition, the pharmacology and therapeutic guidance suggested by the Korean Association for the Study of the Liver were reviewed for entecavir and adepovir, the most frequently prescribed anti-HBV drugs. For influenza, oseltamivir is commonly used despite debates on neuropsychiatric safety issues and zanamivir may be used when an inhalation form is necessary. Although currently used drugs show considerable clinical efficacy, efforts to optimize their use and further research to find new molecules that may overcome their limitations are necessary.
Adenine ; Antiviral Agents ; Communicable Diseases ; Guanine ; Hepatitis ; Hepatitis B ; Influenza, Human ; Inhalation ; Korea ; Liver ; Organophosphonates ; Oseltamivir ; Primary Health Care ; Zanamivir