Case study II

PK Modeling, Oral delivery

1. An HIV positive patient was seen at the ER with lesions that biopsy showed were not Kaposi's Sarcoma but rather bacillary angiomatosis, that may look like KS.  While KS is treated with chemotherapy and or radiation therapy, bacillary angiomatosis is treated with erythromycin. A 250 IV bolus dose of erythromycin was given to a patient prior to sending him home with a handful of prescriptions and samples. Erythromycin is partially excreted as parent drug and as a primary metabolite. Draw the black box diagram that would represent this system. Write the differential equations that would model the amount of erythromycin in the body and urine at any time (t). The patient was dosed with 30 mg. The rate constant to form the metabolite is 0.493 hr^-1, the rate constant for the excretion of metabolite is 0.09 hr^–1 and the rate constant for excretion of unchanged parent drug is 0.087hr ^-1.

What is the amount of metabolite and parent drug in this person at 2 hours?

What should you be aware/alert for with this type of patient?

2. A person on oral Valproate, an anticonvulsive medication, wants to know when they should expect a maximum therapeutic effect. They just took a 250mg tablet.
1. Calculate the time to reach a maximum Cp based on the manufacturer’s (Abbott) literature that the absorption rate constant is 0.7 hr^-1 and the elimination rate constant is 0.065 hr^-1.

b. If another formulation has ka= 0.493 and ke=0.0655h^{-1 are} the formulations bioequivalent?