Department of Medicinal Chemistry, University of Florida, Gainesville, Florida, USA.
Drug Dev Ind Pharm. 2013 Sep;39(9):1494-7. doi: 10.3109/03639045.2012.694590. Epub 2012 Jun 8.
The maximum fluxes (J(M)) of nicotinic acid esters (NAE) across silicone membranes from water (J(MPAQ)) have been measured to determine how well they correlate with J(M) of NAE across human skin from water in vitro (J(MHAQ)) and in vivo (J(MHAQ1)) and with J(M) of NAE across hairless mouse skin from water (J(MMAQ)).
The NAE were all commercially available. Solubilities in water (S(AQ)), isopropyl myristate (S(IPM)) and octanol (S(OCT)) were obtained from literature sources. J(MPAQ) were measured at saturation for all the esters except the methyl ester. In that case, flux was measured at a concentration (C) less than saturation (J(PAQ)) and converted to J(MPAQ) = (J(PAQ))(S(AQ)/C(AQ)).
J(MPAQ) values predicted from the previously reported coefficients to the parameters in the Roberts-Sloan (RS) equation (PRE J(MPAQ)) were substantially lower than the experimental J(MPAQ) values (EXP J(MPAQ)) values obtained here. The EXP J(MPAQ) were incorporated into the previous J(MPAQ) database and new coefficients were obtained: x = -1.837; y = 0.742; z = 0.00435; r² = 0.86. Correlation of J(MPAQ) values with J(MHAQ), J(MHAQ1), and J(MMAQ) values show the same trend as the J(MPAQ) values.
The inclusion of the NAE n = 6 data into the previous n = 32 database for the permeation of the prodrugs through a silicone membrane from water (J(MPAQ)) greatly improved the fit of the n = 38 database to the RS equation: r² = 0.86 vs r² = 0.77. The correlation between log J(MHAQ) and log J(MPAQ) gave r² = 0.98. This suggests that J(MPAQ) values are good predictors of J(MHAQ) values.
测量了烟碱酸酯（NAE）穿过硅橡胶膜从水中的最大通量（J（MPAQ）），以确定其与体外（J（MHAQ））和体内（J（MHAQ1））从水中穿过人体皮肤的 NAE 最大通量以及从水中穿过无毛小鼠皮肤的 NAE 最大通量（J（MMAQ））的相关性如何。
所有 NAE 均为市售产品。文献中获得了在水中（S（AQ））、肉豆蔻酸异丙酯（S（IPM））和辛醇（S（OCT））中的溶解度。除甲酯外，所有酯的最大通量均在饱和条件下进行测量。在这种情况下，通量在低于饱和浓度（J（PAQ））下进行测量，并转换为 J（MPAQ）=（J（PAQ））（S（AQ）/C（AQ））。
根据先前报道的参数对 Roberts-Sloan（RS）方程参数的系数（PRE J（MPAQ））预测的 J（MPAQ）值远低于此处获得的实验 J（MPAQ）值（EXP J（MPAQ））。将 EXP J（MPAQ）值纳入先前的 J（MPAQ）数据库，并获得了新的系数：x = -1.837；y = 0.742；z = 0.00435；r² = 0.86。与 J（MPAQ）值的相关性表明，与 J（MHAQ）、J（MHAQ1）和 J（MMAQ）值的相关性与 J（MPAQ）值的相关性相同。
将 NAE n = 6 的数据纳入先前 n = 32 的数据库中，用于从水中穿过硅橡胶膜的前药渗透（J（MPAQ）），极大地提高了 n = 38 数据库对 RS 方程的拟合度：r² = 0.86 对 r² = 0.77。log J（MHAQ）和 log J（MPAQ）之间的相关性给出 r² = 0.98。这表明 J（MPAQ）值是 J（MHAQ）值的良好预测因子。
