Lec 2- Calculations

Question 1

Doses based on BSA (body surface area)

Answer 1

• BSA can be a better indicator of metabolic mass than body weight because it is less affected by abnormal adipose mass (fat)
• In dose calculations it is mainly used for chemotherapy (cancer and infection) as well as glucocorticoid dosing
• There are a number of ways of estimate BSA. All calculate to units of square metres
• The method used in the GPhC pre-registration examination is mosteller (1987)- others include Duois and Dubois (1916) and Haycock, Schwartz and Wisotsky (1978)

Question 2

The Mosteller formula

Answer 2

• BSA (m²) = Sqaure root (Height (cm) * Weight (Kg)/3600)
• Example: A baby is 2 month old and weighs 5.4kg at a height of 60cm. She is prescribed caspofungin, to treat invasive candidiasis at a dose of 25 mg/m² OD. What dose will she receive
• BSA= Sq.root(60 x 5.4)/3600 = 0.3
• 0.3 x 25 = 7.5 mg

Question 3

Ideal Body Weight (IBW)

Answer 3

• Most dose calculations by body weight are based on actual body weight (ABW)
• In some cases, ideal body weight is more appropriate e.g. adult patient whose ABW is > or < than the average body weight (70kg)
• Ideal body weight can be estimated from the patients height (cm)
• Male IBW = (0.9 x H) - 88kg
• Female IBW = (0.9 x H)- 92 kg

Question 4

Drug absorption

Answer 4

• Bioavailability (F): the fraction of a drug that reaches the systemic circulation (0 to 1)
• Salt Fraction (S)- the fraction of the administered dose that is active drug (e.g. drug in salt or ester form)
• Amount of drug reaching systemic circulation= F x S x Dose
• Dose = Amount absorbed / F x S

Question 5

Volume of distribution (V_d)

Answer 5

• Theoretical volume to distribute a drug if it were found at the same concentration throughout the body as that is serum
• V_d= amount of drug systemically absorbed/ Serum conc (C)
• Amount of drug reaching systemic circulation = F x S x Dose
• Vd = (F x S x Dose)/ C

Question 6

Loadig dose

Answer 6

• An initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose
• Amount of drug in body= Target conc (Cs) v Vd
• Loading dose = amount of drug in the body / FxS
• Loading dose = (C_s x V_d)/ F x S

Question 7

Drug clearance

Answer 7

• Drugs are cleared by excretion and metabolism- the overall process generally follows first-order kinetics
• Drug clearance is the volume of plasma cleared of the drug in unit time (usually one hour)
• If zero order, clearance is a constant
• Some drugs, depend heavily upon renal function for excretion. In this case, the renal function becomes a limiting process (digoxin & gentamicin dependant on renal excretion)
• Renal function is assessed by estimated glomerular filtration rate (GFR)

Question 8

Elimination Half-life

Answer 8

• The time taken for the plasma concentration to fall to half its original value
• 95% of drugs follow first order kinetics- elimination rate is proportional to serum concentration
• Thus 50% of the drug is eliminated in each half life and this remains constant with time

Question 9

Example of elimination rate

Answer 9

Question 10

Maintenance dose

Answer 10

• Amount of drug to keep the serum concentration at steady state (C_ss)
• Amount of drug removed= Cl x C_ss (unit time)
• Maintenance Dose= Amount of drug removed / F x S
• Maintenance dose ever t hours = (Cl x C_ss x t)/ F x S

Question 11

The alligation method

Answer 11

• Used when mixing 2 products of different % strengths of the same active ingredient to produce a 3rd product
• The method applies to liquids or semi-solids (creams and ointments)
• The percentage concentration of the mixed products can vary between zero (pure solvent or base) and 100 (pure active product)
• You will have the percentage strength of the 2 products and the resultant mixture AND the amount (Vol and Wt) of one of these three

Question 12

The alligation method

Answer 12

• You have in stock a 1% hydrocortisone ointment and a 2.5% hydrocortisone ointment
• You need 120g of a 2% ointment how much of each stock will you need to use?

Question 13

Displacement Value

Answer 13

• The number of parts by weight of drug that displaces one part by weight of base
• If DV= 1 then the drug has the same density as the base. The higher the drug density the less the DV
• Used for solid preparation e.g. suppositories that are prescribed by unit weight
• Amount of base= (N x W) - (N x w)/DV
• N= Number of suppositories
• W= mould calibration
• w= Weight active ingredient in 1 suppository
• DV= displacement value

Question 14

Displacement volume

Answer 14

• Volume of solvent displaced when a known amount of drug is dissolved
• Most significant when small volumes involved
• Usually expressed as mL/100mg or mL/10mg