The equation that defines the rate of change or rate of accumulation of drug in the body 

dA/dt = Rate of Input (k₀) – Rate of Output (KA)

dA/dt = k₀ – KA

Can be rewritten as....

dA/dt = k₀ – (Cl_t x Cp)

Cl_t  x Cp_ss

                          Cl_t = k₀ / Cp_ss

There are two ways to determine the overall rate of infusion.  This is, either divide the total amount intended for infusion by the interval of infusion, or by multiplying the intended steady state level by the total body clearance.

These two equations would be....... 

k₀ = dA/dt = mass/time

k₀ = Cp_ss x Cl_t

One approach in achieving the steady-state level of a drug immediately is to give a loading intravenous bolus dose with simultaneous intravenous infusion. To determine the loading dose we assume the steady state level is equal to the initial plasma concentration of the loading dose i.e, set Cp_ss = Cp° . The loading dose would then be equal to:

The combination of intravenous bolus and infusion can be represented as:

Rate of Absorption = k_a  x A_D

This represents the total amount absorbed or total amount of absorbable drug.

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variable in equation is K_at

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When k_a is much greater than K, the value of T_max is solely a function of the absorption rate constant and inversely proportional to it.

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According to this equation, the maximum plasma concentration is directly proportional to the total amount absorbed, FD, and the fraction of dose in the body at T_max (i.e.,  f_bmax = e^-KTmax). Thus, the maximum amount of drug in the body is:

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The area under plasma concentration-time curve is another important parameter of oral absorption and it is considered a sensitive indicator of the amount of drug that ultimately reaches the systemic circulation. Its magnitude is directly proportional to the total amount absorbed. Therefore equal doses of a drug should provide equal AUCs. This parameter is very useful in determining the bioavailability and bioequivalence of therapeutic agents 

[image]clearance

[image]Volume of distribution

- Oral administration

- Sublingual

- Buccal

- Inhalation

- Injection into the body but not into the vascular system

- Administration through a natural orifice 

- Various regional pH of GI tract and the pKa of the drug

- Gastric emptying process

- Intestinal motility or small intestinal transit time (SITT)

- First pass extraction (hepatic or GI)

- Intestinal metabolic enzymes such as Cytochrome P450 3A4

- P-Glycoprotein

- Food

- Disease states

- Other factors 

- Passive Diffusion

- Transcellular Diffusion

- Paracellular Diffusion

- Carrier-mediated Transcellular Diffusion (also known as facilitated diffusion)

- Transcellular Diffusion Subject to P-Glycoprotein Efflux

- Active Transport

- Pinocytosis

- Solvent Drag

- Ion-pair absorption 

The following factors influence the distribution of drugs:

- Blood Flow

- Extent of binding to plasma proteins

- Physicochemical characteristics of drugs

- The degree and extent to which drugs penetrate through physiological barriers

- The extent of elimination that continuously removes the drug from the body and competes with the distribution phenomena. 

- Placental transfer

- Blood Brain Barrier

- Blood Testis Barrier

- Blood Aqueous Humor Barrier

- Blood Lymph Barrier 

- Oxidation of carbon-carbon double bond

- Oxidation of alcohols

- Oxidation of aromatic carbons

- Oxidation of nitrogen-containing functional group

- Oxidative deamination

- Oxidative N-, O-, and S-dealkylation

- Other oxidative reactions 

- Flavin monooxygenase

- Alcohol dehydrogenase

- Monoamine oxidase

- Diamine oxidase

- Aldehyde dehydrogenase

- Xanthine oxidase