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청소율 모델: 구획 모델
청소율은 혈장과 신장, 간과 같은 고관류 장기를 포함한 중앙 구획에서 약물 제거를 측정합니다. 계산은 약동학 모델과 투여 경로에 따라 다릅니다. 예를 들어, 1구획 모델은 정맥 주사로 투여되고 소변으로 쉽게 배출되는 아미노글리코사이드 항생제와 같은 극성 약물의 약동학을…
클리어런스(clearance)는 혈장과 신장 및 간과 같은 고도로 관류된 장기로 구성된 중앙 구획에서 약물 제거를 직접 측정합니다.
허가율 계산은 약동학 모델과 투여 경로에 따라 다릅니다.
단일 구획 모델은 아미노글리코시드 항생제와 같은 극성 약물의 약동학을 정맥 주사하고 소변으로 쉽게 배설하는 것을 설명합니다.
여기서 단자 속도 상수, λz 및 총 분포 부피의 곱인 Vss는 여유 공간을 제공합니다.
경구용 약물의 흡수가 제거보다 빠르면 말단 속도 상수는 제거를 나타냅니다. 그러나 플립플롭 현상에서 구강 흡수가 제거보다 느리면 속도 상수는 대신 흡수를 반영합니다.
2-compartment 모델은 혈액 관류가 잘 되지 않은 compartment에 분포된 극성이 적은 약물의 약동학을 정확하게 나타냅니다. 임상적으로 항생제 반코마이신의 약동학은 이 모델에 의해 효과적으로 예측됩니다.
특히, 분포 청소는 두 구획, 즉 혈장과 관류가 잘 된 기관을 포함하는 중앙과 관류가 적은 기관을 수용하는 말초
부 사이의 청소를 반영합니다.View the full transcript and gain access to JoVE Core videos
Q1: What does clearance measure in pharmacokinetics?
Clearance directly measures drug elimination from the central compartment, which comprises plasma and highly perfused organs like kidneys and liver. It quantifies how efficiently the body removes a drug and is essential for determining appropriate dosing regimens to maintain therapeutic drug levels while minimizing potential side effects.
Q2: How does the one-compartment model calculate drug clearance?
In the one-compartment model, clearance is calculated as the product of the terminal rate constant (λz) and total volume of distribution (Vss). This model effectively describes polar drugs like aminoglycoside antibiotics administered intravenously and readily excreted in urine, making it ideal for drugs with rapid, uniform distribution.
Q3: What is the flip-flop phenomenon in oral drug pharmacokinetics?
The flip-flop phenomenon occurs when oral drug absorption is slower than elimination. In this case, the terminal rate constant reflects absorption kinetics rather than elimination kinetics, potentially altering clearance calculations and requiring careful interpretation of pharmacokinetic parameters for accurate dosing.
Q4: Why is the two-compartment model used for less polar drugs?
The two-compartment model accurately represents pharmacokinetics of less polar drugs that distribute into poorly blood-perfused compartments. Vancomycin, a clinically important antibiotic, is effectively predicted by this model because it accounts for both central and peripheral compartment distribution, providing more accurate clearance predictions.
Q5: What is distributional clearance and how does it differ from total clearance?
Distributional clearance reflects drug movement between two compartments: the central compartment including plasma and well-perfused organs, and the peripheral compartment housing less-perfused organs. Unlike total clearance, which measures elimination from the body, distributional clearance describes the rate of drug redistribution between tissue compartments.
Q6: How does administration route affect clearance calculations in compartment models?
Clearance calculations vary depending on the administration route and pharmacokinetic model used. Intravenous administration with the one-compartment model provides straightforward clearance from the product of terminal rate constant and volume of distribution, while oral administration requires consideration of absorption kinetics and potential flip-flop phenomena.
Q7: What organs comprise the central compartment in clearance models?
The central compartment includes plasma and highly perfused organs such as kidneys and liver. These organs receive rapid blood flow and are where most drug elimination occurs, making them critical for understanding how clearance directly measures drug removal from this compartment.