Acyclovir drug transport

Receptor-mediated transporters are excipients that serve as substrates to exploit specific receptors present on cell membranes. Examples of various receptors that have been explored for permeation enhancement include bile acids (45), vitamin Bi2 (46), amino acids (47), and folic acid (48). Most of the work in receptor-mediated transporters is conducted via the use of prodrugs. For example, a prodrug of acyclovir conjugated to bile acids was seen to have higher permeability as compared to the original drug, because of receptor-mediated transport of the prodrug via bile acid transporters (49). 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

Uptake transporter prodrug substrates have been used to improve drug absorption through GI tract. The most successful example is an antiviral prodrug valacyclovir, which shows oral bioavailability three to live times greater than its parent drug acyclovir (Weller et al., 1993). The increased oral bioavailability is attributed to PEPTl-mediated absorption, which was demonstrated by in situ rat perfusion model, Caco-2 cells, and PEPTl-transfected CHO cells (Balimane et al., 1998). 

An in vitro and in vivo study showed a drug interaction between penicillin and acyclovir by means of inhibition of OATl and OATS transporters, subsequently decreasing the renal excretion of acyclovir. Patients should be monitored closely for acyclovir adverse effects when given in combination with penicillin [45 ]. 

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