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Toxicokinetics
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
The pKa of a drug, therefore, is defined as the pH at which 50% of the compound is ionized. Similarly, pKb is the negative logarithm of the base dissociation constant (Kb). In general, acids and bases are classified according to their ability to dissociate relative to the pH of the solution. Independently of the pH, however, the lower the pKa of an acid, the stronger the acid. Similarly, the lower the pKa (or the higher the pKb) of a base, the stronger the base. Most therapeutic drugs are weak acids, weak bases, or neutral or amphoteric compounds.
Skin Absorption Databases and Predictive Equations
Published in Richard H. Guy, Jonathan Hadgraft, Transdermal Drug Delivery, 2002
Brent E. Vecchia, Annette L. Bunge
The fraction of nonionized compound in the vehicle, fni, for compounds with one dominant acid-base reaction, can be calculated from the acid-base dissociation constant (pKa) and the vehicle pH (6):
Published population pharmacokinetic models of valproic acid in adult patients: a systematic review and external validation in a Chinese sample of inpatients with bipolar disorder
Published in Expert Review of Clinical Pharmacology, 2022
Yan-Nan Zang, Wei Guo, Fang Dong, An-Ning Li, Jose de Leon, Can-Jun Ruan
Serum concentrations of VPA were analyzed by a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method in the hospital TDM laboratory. Table 1 describes many prior VPA studies that used immunoassay methods. As VPA has an acid-base dissociation constant (PKa) of 4.6 and other drugs co-administered and PKas >7, they are easily separated in our UPLC-MS/MS method. In our lab, we compared the UPLC-MS/MS method with fluorescence polarization immunoassay (FPIA) and they had comparable VPA concentrations, but the data was not published. On the other hand, Zhao et al. [61] compared UPLC-MS with three other methods: FPIA, chemiluminescence microparticle immunoassay (CMIA), and high-performance liquid chromatography (HPLC) methods; the UPLC-MS method correlated well and displayed comparable VPA concentrations.
Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo
Published in Drug Delivery, 2020
Wanfu Men, Peiyao Zhu, Siyuan Dong, Wenke Liu, Kun Zhou, Yu Bai, Xiangli Liu, Shulei Gong, Shuguang Zhang
To measure the base dissociation constant (pKb) of polymer PBAE, potentiometric titration was operated as reported (Fernando et al., 2018). Briefly, the PBAE was dissolved in deionized water at pH 3.0. Then, sodium hydroxide (NaOH) solution was added dropwise into the mixed solution, and the real-time pH values were recorded by an automatic titration titrator (Hanon T-860, Jinan, China). The pKb value of PBAE was determined according to the plots of pH value against the volume of NaOH solution.