Abstract
Objective: A new compound of salicylic acid derivative, namely 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3CBB), was synthesized to find a compound exhibiting higher analgesic activity and smaller ulcer irritation than acetylsalicylic acid (ASA). Therefore, this study aimed to investigate the pharmacokinetics of this new compound in rats, following a single dose oral administration of 3CBB (45 mg/kg BW).
 Methods: Plasma samples of 9 healthy rats were collected before and up to 3 h after its oral administration, following an 18 h fasting period. Plasma concentrations of 3CBB were determined using a validated HPLC-DAD assay. Pharmacokinetic parameters were determined using the compartment model technique. All experiments were carried out in triplicate.
 Results: The pharmacokinetic parameters of 3CBB obtained were as follows: Tmax= 28.9±1.1 min, Cmax = 0.57±0.02 µg/ml, AUCtotal = 66.3±1.0 µg min/ml, Kel = 0.018±0.002 min-1, and T1/2el = 39.4±3.9 min. The long elimination half-life and low Cmax indicated that 3CBB was extensively distributed in the deep and very deep tissues. This confirmed the unique and special characteristics of a highly lipophilic compound like 3CBB (log P = 3.73).
 Conclusion: 3CBB demonstrated a slower onset of action and longer elimination time from the body compared to ASA. Thus this new compound is a potential candidate to be developed as a new drug.
Highlights
Acetylsalicylic acid (ASA, aspirin) has been used as a non-steroidal anti-inflammatory drug and antiplatelet agent for decades
To maintain the benefit of acetylsalicylic acid (ASA) and minimize its harmful effect, we have modified the structure of salicylic acid, by replacing the acetyl group with the benzoyl group, yielding a compound known as 2-((3(chloromethyl)benzoyl)oxy)benzoic acid (3CBB)
A typical HPLC chromatogram demonstrating the peaks associated with blank plasma, 3CBB, and internal standard is shown in fig
Summary
Acetylsalicylic acid (ASA, aspirin) has been used as a non-steroidal anti-inflammatory drug and antiplatelet agent for decades. ASA is highly bound by plasma protein (99%) It is hydrolyzed primarily in the liver, yielding salicylic acid. The pharmacokinetic profile of ASA in rats after oral administration (40 mg/kg BW) was reported, with the following parameters area under the plasma concentration versus time curve from zero to infinity (AUC 0-∞) = 152.2 μg min/ml, elimination half-life (T1/2) = 5.66 min, peak plasma concentration (Cmax) = 9.74 μg/ml, and time to reach maximum drug concentration in plasma (Tmax) = 7 min [3]. Other study reported the pharmacokinetics of ASA in human plasma after oral administration (500 mg/70 kg BW), with the following parameters: AUC 0-∞ = 5.12 mg h/ml, T1/2 = 0.422 h, Cmax = 4.84 μg/ml, Tmax = 0.5 h [4]. To maintain the benefit of ASA and minimize its harmful effect, we have modified the structure of salicylic acid, by replacing the acetyl group with the benzoyl group, yielding a compound known as 2-((3(chloromethyl)benzoyl)oxy)benzoic acid (3CBB) (fig. 1)
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