Effect of Charge on Renal Clearance

Similar patterns occur for acidic and basic drugs, however, tubular pH is often more acidic (pH 6.5) than plasma. Because of this, acidic drugs are reabsorbed more extensively and basic drugs less extensively than their log D74 would suggest. Moreover, much greater rates of excretion/clearance can occur for these charged moieties due to the tubular active transport proteins. The effects of tubular secretion are particularly apparent as lipophilicity increases (as indicated by the structural features required by the transport systems described above) but before substantial tubular reabsorption occurs. With the shift in tubular pH the value of 0 as a threshold for reabsorption for neutral drugs (see Figure 6.1) correlates to a value of - 1 for acid drugs and + 1 for basic drugs. These effects are illustrated in Figure 6.2.

Figure 6.2 highlights the role of lipophilicity in the active transport of drugs. Peak values for renal clearance for these compounds occur at log D74 values between - 2 and 0. These values span the region where the compounds have sufficient lipophilic-ity to interact with the transport proteins but are not substantially reabsorbed.

Figure 6.2 highlights the role of lipophilicity in the active transport of drugs. Peak values for renal clearance for these compounds occur at log D74 values between - 2 and 0. These values span the region where the compounds have sufficient lipophilic-ity to interact with the transport proteins but are not substantially reabsorbed.

Was this article helpful?

0 0

Post a comment