**Type V**

These are pseudo allergic reactions, that resemble allergic reactions clinically, but for which no immunological basis can be found, e.g. asthma and skin rashes caused by aspirin. Admin‐ istration of ampicillin or amoxicillin causes a skin rash which resembles the one caused by penicillin hypersensitivity. The ampicillin-caused rash can be distinguished from penicillin hypersensitivity on the basis of two features; it has a later onset, typically ten to fourteen days, compared to penicillin sensitivity which comes between seven to ten days. Furthermore, the sensitivity does not recur following re-exposure to ampicillin and is not as serious as the one caused by penicillin.

inline formula rfpt=1-0.56 (1-0.33) = 0.62

Clpt= Clnl.rfpt

1 – *ex p* (−*KT* )

i.e. 1 - e-KT = 1 - 2.71-0.086 x 6 = 1 - 0.596 = 0.4.

*Cssmin* = *<sup>F</sup> <sup>x</sup> dose* / *Vss*(*ex p* <sup>−</sup>*kt*)

F x dose/Vss 1 – exp(-kT)

= 3.4ml.min-1kg-1x 0.62

has Vss = 0.5 L/kg, effective concentration is 12mg/L and that

changing of the dosage interval to 6 hours would affect Cssmin.

interval and is equal to 0.35 and Css min = Css max.exp(-kt). Therefore,

**2.** Write an essay on bioprospecting for new antimicrobial agents.

Given the following characteristics of drug A; t½ = 8h, given at a dosage of 450mg every 12h,

Introduction to Biochemical Pharmacology and Drug Discovery

http://dx.doi.org/10.5772/52014

513

Determine the Cssmin and Cssmax for a 60 kg patientif F = 1 and expKT = 0.35. Explain how

The term exp(-KT) is the fraction of the last dose that remains in the body at the end of a dosing

1- 0.35 =15/0.65 x 0.35 ~ 8.0 mg/L while Cssmax =15/0.65=23 mg/L

The predicted minimum of 8.0mg/L is below the effective concentration to achieve efficacy. Therefore the dosing interval should be reduced. A reduction of the interval to, say, six hours, increases denominator and therefore causes an increase of Cssmin. Since t1/2 = 0.693/K, K = 0.086

The new Css minimum becomes; = 450/30 x 0.4 = 15 mg/L which is within the required thera‐

**1.** Write an essay on statistical considerations that guide clinical evaluation of new drug

**3.** Drug clearance must always be adjusted for alterations of renal function using the formula: rfpt = 1- fenl (1- rfxpt), explain what each term in the above equation represents. Consequently, calculate the clearance of acetaminophen (panadol) in a 70 kg patient with depressed renal function given the following; normal clearance = 350 ml min -170 kg; fenl = 0.56. The patient creatinine clearance = 80 mlmin-1 70 kg. Normal creatinine clearance = 120 ml min-1 70 kg. What effect would the impaired renal function have on dosing interval?

= 2.1ml.min-1kg-1

inline formula

Problem 6

Css, max =

**Solution**

Cssmin = 450/30 x 0.35

peutic concentration.

**Review exercise**

agents
