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Review
. 2016 Dec;55(12):1495-1505.
doi: 10.1007/s40262-016-0409-0.

A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration

Parag Kumar  1   2 , Emily Thudium  1 , Kevin Laliberte  1 , David Zaccardelli  1 , Andrew Nelsen  3
Affiliations
Review

A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration

Parag Kumar et al. Clin Pharmacokinet. 2016 Dec.

Abstract

Treprostinil is available in three different formulations and four different routes of administration: Remodulin® (treprostinil sodium, intravenous and subcutaneous administration), Tyvaso® (treprostinil sodium, inhaled administration), and Orenitram® (treprostinil diolamine, oral administration) for the treatment of pulmonary arterial hypertension (PAH). Pharmacokinetic studies have been performed in healthy volunteers and patients with PAH. The intent of this review is to outline pharmacokinetic considerations of the three treprostinil formulations and provide clinicians with a resource that may support clinical decisions in treating patients with PAH.

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Conflict of interest statement

Compliance with Ethical StandardsFundingNo external funds were used in the preparation of this manuscript.Conflicts of interestParag Kumar and Emily Thudium completed post-doctoral fellowships with United Therapeutics and Parag Kumar is currently employed by the National Institutes of Health. Kevin Laliberte, David Zaccardelli, and Andrew Nelsen are employees of United Therapeutics Corp.

Figures

Fig. 1
Fig. 1
Mean plasma concentration of treprostinil following intravenous and subcutaneous infusion: a linear plot and b log-linear plot [14]. IV intravenous, SC subcutaneous
Fig. 2
Fig. 2
Mean (±standard deviation) plasma treprostinil concentration vs. time following administration of 54 μg of inhaled treprostinil (n = 11) [18]
Fig. 3
Fig. 3
Impact of co-administered drugs on the systemic exposure of oral treprostinil 1 mg compared with oral treprostinil administered alone [28]. AUC ∞ area under the plasma concentration–time curve from time zero to infinity, bid twice daily, CI confidence interval, C max maximum concentration, PK pharmacokinetics, qid four times daily, tid three times daily
Fig. 4
Fig. 4
Mean ± standard error of the mean treprostinil concentration vs. time plots by treatment regimen (semi-log). Tyvaso® has been omitted from this figure as its systemic effects are not comparable with parenteral Remodulin® or oral treprostinil (Data on file). Mean dose ± standard deviation of Remodulin® (n = 32): 58.2 ± 19.2 ng/kg/min; total daily mean dose ± standard deviation of oral treprostinil twice daily (n = 6): 27 ± 12.3 mg; total daily mean dose ± standard deviation of oral treprostinil three times daily (n = 26): 37.9 ± 13.8 mg. bid twice daily, tid three times daily. Data from a study sponsored by United Therapeutics Corp. The PK report from this study was dated Feb 2015
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References

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