Pharmacokinetics of ketoprofen enantiomers after different doses of the racemate.

Abstract

The pharmacokinetics of the enantiomers of ketoprofen after oral administration of 12.5 mg, 25 mg and 50 mg and i.v. administration of 50 mg racemic ketoprofen to 24 healthy subjects were investigated. The AUC values of R-(r2 = 0.929) and S-ketoprofen (r2 = 0.930) were proportional to dose. The absolute bioavailability of the 50 mg oral dose was 84.5 (s.d. 20.6) % and 81.4 (18.0) % for R-ketoprofen and S-ketoprofen, respectively. With the exception of AUC values no dose dependent differences in pharmacokinetic parameters were observed. However, the R-enantiomer had higher AUC, lower clearance data and higher Cmax values than the S-form after oral administration. The results suggest that stereochemical and pharmacokinetic considerations cannot explain the lack of dose response observed with ketoprofen doses below 50 mg.

The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC

“…The physicochemical and biopharmaceutical properties of ibuprofen, ketoprofen, carvedilol, ketoconazole, danazol, and fenofibrate used in the GastroPlus™ simulations, as well as the chemical, physiological, and pharmacological parameters for drugs cited in the literature are presented in Table 1 (Abernethy and Greenblatt, 1985; Avdeef et al, 1998; Baxter et al, 1986; Beetge et al, 2000; Cordero et al, 1997; Domanska et al, 2009; Dressman and Lennernäs, 2000; Fei et al, 2013; Geisslinger et al, 1995; GlaxoSmithKline, 2009; Hooper et al, 1991; Huang et al, 1986; Ige et al, 2013; Kasim et al, 2004; Keating and Croom, 2007; Loftsson et al, 2008; Mannisto et al, 1982; Oliary et al, 1992; Peeters et al, 2008; Perez de la Cruz Moreno et al, 2006; Planinsek et al, 2011; Prajapati et al, 2012; Vertzoni et al, 2010; Yun et al, 2006). Since the size of drug particles can significantly affect drug dissolution rate, the relatively larger particle size, a radius of 25 μm, to minimize the particle effects for dissolution was set as the mean particle size with a coefficient of variation (Le et al, 2006; Lin et al, 1982; Mutalik et al, 2008; Sheng et al, 2008; Takano et al, 2008; Tsume and Amidon, 2010).…”

“… Vc; Volume of Central Compartment. A Calculated by GastroPlus™ 7.0. B Calculated by ADMET Predictor. a Oliary et al (1992). b Perez de la Cruz Moreno et al (2006). c Avdeef et al (1998). d Domanska et al (2009). e Abernethy and Greenblatt (1985). f Geisslinger et al (1995). g Cordero et al (1997). h Beetge et al (2000). i Kasim et al (2004). j GlaxoSmithKline (2009). k Planinsek et al (2011). l Loftsson et al (2008). m Huang et al (1986). n Vertzoni et al (2010). o Peeters et al (2008). p Mannisto et al (1982). q Baxter et al (1986). r Keating and Croom (2007). s Fei et al (2013). t Ige et al (2013). u Yun et al (2006). v Hooper et al (1991). w Prajapati et al (2012). x Dressman and Reppas (2000). …”

Elucidating the Role of Dose in the Biopharmaceutics Classification of Drugs: The Concepts of Critical Dose, Effective In Vivo Solubility, and Dose-Dependent BCS

“…In Fig. 5b are illustrated the data for ketoprofen (35,36) which demonstrate a dose linearity. The AUC 0-∞ ketoprofen data that were plotted (Fig.…”

“…Plots of (a) diclofenac and (b) ketoprofen (S enantiomer) presenting AUC vs dose data after oral (•) and iv (∇) administration (data taken from refs(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen

“… Vc; Volume of Central Compartment # Calculated by GastroPlus™ 7.0 * Calculated by ADMET Predictor a Ref [13] b Ref [23] c Ref [20] d Ref [21] e Ref [19] f Ref [22] g Ref [25] h Ref [24] …”