The polyene antifungal amphotericin B (AMPH-B) is considered to be an excellent antifungal option for its broad antifungal activity and potent fungicidal potential, and its use rarely results in resistant organisms. AMPH-B, however, also is known to cause frequent adverse reactions, including renal impairment and hypokalemia that may limit both the duration and dose of administration [1]. Liposomal amphotericin B (L-AMB) was developed to reduce the toxicities of AMPH-B. This product retains AMPH-B in a single-layer liposomal membrane consisting of phospholipids and cholesterol. The pharmacokinetics (PK) and pharmacodynamics (PD) of AMPH-B indicates that its efficacy increases as the ratio of the maximum blood concentration (Cmax) to the minimum inhibitory concentration (MIC) (Cmax/MIC) increases [2], which means that fungicidal action increases in a dose-dependent manner.

L-AMB has much lower toxicity than conventional AMPH-B injections [[3], [4], [5]] and can therefore be given at higher doses. Because liposomes do not readily penetrate healthy blood vessel walls due to a relatively large size of 60–100 nm in diameter, L-AMB minimally distributes to healthy tissue outside of the sites of inflammation. For this reason, normal tissues are not damaged as much, and the drug is efficiently distributed to inflamed tissue where vascular permeability is higher. L-AMB is therefore considered as a drug delivery system that carries greater load of its antifungal cargo to sites of infections [[5], [6], [7], [8]]. The excellent distribution of L-AMB to sites of inflammation has been clinically demonstrated [9,10].

In the field of infection treatment, ample research has been conducted to develop dosing designs for various drugs optimized for individual patients based on the relationship between PK, efficacy and safety. There has been a debate about the need for therapeutic drug monitoring for azole antifungals [11,12]. In contrast, very little research has been done in dosing design in AMPH-B or L-AMB. The factors that influence their PK have yet to be characterized, and no guidance for selecting an appropriate dosage has been established. To address this lack of information, we investigated the relationships between AMPH-B PK and efficacy or safety in patients treated with L-AMB.