How can changes in metabolism as a result of CKD alter the pharmacokinetic behavior of drugs?
Even drugs without or with only minimal kidney elimination can have altered pharmacokinetics in advanced CKD. CKD may increase, decrease, or have no effect on nonkidney clearance.
Some drugs are metabolized to active metabolites that are insignificant with normal kidney function but accumulate in CKD.
For example, morphine metabolizes to 6- and 3-morphine-gluconate with respiratory depression and seizure properties. In CKD the clearance of the parent compound (morphine) is not significantly affected; however, morphine metabolizes to 6- and 3-morphine-gluconate, which accumulate and place patients at risk for serious adverse drug reactions.
Therefore it is recommended that morphine be used cautiously in patients with CKD or avoided completely if high doses or a prolonged use is indicated.
