This tutorial defines the principles of the concentration - effect relationship which are the basis of pharmacodynamics. The two key parameters of pharmacodynamics are the maximum response (Emax) and the concentration producing 50% of Emax (C₅₀). The time course of effect is illustrated under the assumption that drug effects are immediately related to concentration in the central compartment e.g. plasma. The related idea of duration of drug action and its relationship to dose is shown to have a simple relationship with drug half-life.
Half-Life ; Plasma

Regulation for the radiopharmaceuticals should be reasonably different from that of other drugs. Radiopharmaceuticals are always used by compounding based on the doctor's order, have short half life and very low administration dose. Its pharmacological effect is not from its chemical effect but from radiation. The background for exploratory IND (Investigational New Drug) explained by the FDA was to reduce the time and resources expended on candidate products that are unlikely to suceed, new tools are needed to distinguish earlier in the process those candidates that hold promise from those that do not. In this review, basic concept for exploratory IND and RDRC guideline is summarized and various suggestions for improving and expediting procedure for new radiopharmaceutical development would be described.
Half-Life ; Korea* ; Radiopharmaceuticals

Authors have developed highly reproducible calibration method for the Micro-Selection HDR Ir-192 system(Nucletron, Netherland). The new jig has a 10cm radius circular hole in the 30cm x 30cm x 0.2cm acrylic plate, and 5F flexible bronchial tubes are attached around the hole. The source moves along the circle in the tubes an? the ionization chamber is placed vertically at the center of the circular hole(center of the jig). Dose distribution near the center was derived theoretically, and measured with the film dosimetry system. Theoretical calculation and measurement show the error margin below 0.1% for 1mm or 2mm position deviation. We have measured at 12 and 24 points of circle with 1, 6, 11 and 21 second dwell time of source in order to calculate the activity of the source. Measurements have been repeated daily for 50 days. The accuracy and the reproducibility are below 1% error margin. The half life of the source from our measurement is estimated 73.4+/-0.4 days.
Calibration* ; Film Dosimetry ; Half-Life ; Radius

Pharmacokinetics is the study of the rate and degree of drug transport to various tissues in the human body. Pharmacokinetic parameters summarize drug kinetics and ideally predict a clinical situation. A single kinetic profile may be summarized by peak concentration, peak time, half-life and area under the curve. Dosage regimens are designed to confer the maximum desired effects for the required time period with minimal toxicity. Target-controlled infusions use pharmacokinetic models to titrate intravenous anesthetic administration to achieve a desired drug concentration. Context-sensitive half time is used to predict the clinical time course, rather than terminal half-life. It is important that anesthesiologists understand the basic pharmacological principles and apply them in their daily clinical practice. This review discusses the ways in which anesthesiologists can design a patient-specific dosage regimen of intravenous anesthetics by utilizing basic concepts of pharmacokinetics and pharmacodynamics using pharmacokinetic simulations.
Anesthetics, Intravenous ; Half-Life ; Human Body ; Pharmacokinetics*

The effects of CYP1A enzyme on the pharmacokinetics of p-acetaminophen were studied in Bactrian camel. Twelve Bactrian camels were divided into 2 groups, then given a single dose of p-acetaminophen only or with the enzyme inhibitor lomefloxacin. Blood samples were collected after different intervals, and p-acetaminophen concentration was determined by high-performance liquid chromatography. Pharmacokinetic parameters were analyzed by Phoenix WinNonLin v.7.0. The results show that lomefloxacin can significantly inhibit Bactrian camel CYP1A enzyme, as evidenced by the prolonged elimination half-life, increased maximum plasma concentration and area under the curve values and the shortened time to peak concentration for p-acetaminophenol in the substrate with inhibitor group. The results lay a foundation for revealing the particular characteristics of the CYP1A enzyme in Bactrian camels.
Camels ; Chromatography, Liquid ; Half-Life ; Pharmacokinetics ; Plasma

BACKGROUND: Radioiodine treatment is effective for the removal of remnant thyroid tissues after thyroidectomy in patients with differentiated thyroid carcinoma. To induce the elevation of serum TSH level which facilitates the uptake of radioiodine into remnants, a 4 to 6 week interval between thyroidectomy and radioiodine administration has been established. During the period of preparation, most patients have experienced overt symptoms of hypothyroidism which have led to the development of alternative strategies. Some reports have suggested that the interval could be reduced to about 3 weeks with less symptoms. We reevaluated the adequate time needed for the elevation of serum TSH level above 30microU/mL after thyroidectomy. METHODS: Forty five patients who had undergone total thyroidectomy for differentiated thyroid carcinoma were investigated. Serum TSH and free T4 levels were measured one or more times within 3 weeks after operation(total 97 blood samples). Eighty nine blood samples were obtained within 15 days. RESULTS: In 41 patients (91.1%) serum TSH levels increased to 30 microU/mL until 15 days after operation. Until postoperative 21 days, serum TSH levels in all the other patients reached 30microU/mL. In linear equation, the daily increment of serum TSH levels was 2.62microU/mL for the first 8 days after operation and 5.34micorU/mL for the next 7 days. The half-life of serum free T4 levels showed marked individual variations. CONCLUSION: Measurement of serum TSH level at about 15 days after total thyroidectomy for differentiated thyroid carcinoma may be useful in determining the time of radioiodine administration.
Half-Life ; Humans ; Hypothyroidism ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyrotropin

OBJECTIVES: The study was performed to investigate the changes of urinary thiodiglycolic acid (TDGA) concentration in workers exposed to vinyl chloride monomer (VCM) according to the time of sampling urine. METHODS: The personal exposure to airborne VCM was assessed and urinary TDGA concentration was sampled in 31 workers employed in a VCM and polyvinyl chloride (PVC) manufacturing factory. Urinary TDGA was sampled three times: before the start of the shift after 3 days off (TDGA1), after the end of the first-day shift (TDGA2) and before starting the following day shift after completing the oneday shift (TDGA3). Urinary TDGA in 30 workers who had not been exposed to airborne VCM was sampled after the end of the shift. A gas chromatography/pulsed flame photometric detector (GC/PFPD) was utilized to analyze TDGA concentration in urine after the urine was methylated with trimethylsilyldiazomethane(2.0M in diethyl ether). RESULTS: The creatinine level was 0.179+/-0.271 mg/g in the control workers and 0.218+/-0.443 mg/g in the workers before the start of the shift after 3 days off (TDGA1), showing no significant difference (p=0.7035). Urine samples were compared according to sampling time in order to investigate the change of urinary TDGA concentration in the case of continuous exposure to airborne VCM. In VCM-exposed workers, urinary creatinine concentration was 0.434+/-0.623 mg/g in TDGA2 and 0.767+/-1.056 mg/g in TDGA3, which indicated a gradual but significant increase (p=0.024). In terms of the statistical correlation between airborne VCM and urinary TDGA to evaluate exposure dose per day, of the three urinary TDGA concentrations, TDGA3 showed the highest degree of regression (R(2)=0.4215) with 8h-TWA airborne VCM concentration. CONCLUSION: Based on this result, the excretion half-life of urinary TDGA was assumed to be less than 3 days, because the concentration of urinary TDGA at 3 days after exposure to airborne VCM was decreased to the level of urinary TDGA concentration in the control workers. The concentration of urinary TDGA increased in the case of continuous shift, due to the accumulation of residual metabolites of TDGA. It was considered that TDGA3 can be applied as a useful biological index to evaluate the exposure dose of airborne VCM during one day because TDGA3 showed the highest correlation with the exposure dose of airborne VCM in the previous shift day.
Creatinine ; Half-Life ; Humans ; Polyvinyl Chloride ; Vinyl Chloride*

We performed an 18F-fluorodeoxyglucose (FDG) position emission tomography (PET) in two patients with complex partial status epilepticus (CPSE). Ictal FDG studies usually occur by chance, because of the unpredictable nature of seizures and the short half-life of flourine-18. In addition to that, ictal PET studies are often contaminated by postictal hypometabolism due to the relatively long FDG uptake period. We experienced two patients with prolonged states of mental confusion. During the confused state, eletrophysiologic and neuroimaging studies were done to confirm the diag-nosis of CPSE. Ictal PET studies showed hypermetabolism during status epilepticus compared with interictal PET. There has been no case report about ictal PET in Korea. We present two cases of ictal PET with a review of the literature
Half-Life ; Humans ; Korea ; Neuroimaging ; Seizures ; Status Epilepticus*

We performed an 18F-fluorodeoxyglucose (FDG) position emission tomography (PET) in two patients with complex partial status epilepticus (CPSE). Ictal FDG studies usually occur by chance, because of the unpredictable nature of seizures and the short half-life of flourine-18. In addition to that, ictal PET studies are often contaminated by postictal hypometabolism due to the relatively long FDG uptake period. We experienced two patients with prolonged states of mental confusion. During the confused state, eletrophysiologic and neuroimaging studies were done to confirm the diag-nosis of CPSE. Ictal PET studies showed hypermetabolism during status epilepticus compared with interictal PET. There has been no case report about ictal PET in Korea. We present two cases of ictal PET with a review of the literature
Half-Life ; Humans ; Korea ; Neuroimaging ; Seizures ; Status Epilepticus*

Blood substitutes, especially red blood cell (RBC) substitutes, have been developed for the past five decades and have several advantages over allogenic packed RBCs, including a prolonged half-life, lack of a cross-matching requirement, and minimal infection risk or concerns about immunologic reactions. There are two main groups in RBC substitutes: perfluorochemicals and hemoglobin-based oxygen carriers (HBOCs). HBOCs are made of hemoglobins from: human, bovine or recombinant and undergo three modification types: chemical (intramolecular cross-linking, polymerization, conjugation to macromolecules and combination of several chemical modifications), genetic, or technological (microencapsulation). The types, side effects, current status of clinical trials, and the future of HBOCs are described in details.
Blood Substitutes ; Erythrocytes ; Half-Life ; Hemoglobins ; Humans ; Oxygen ; Polymerization ; Polymers