Pharmacokinetics of Succinylated Serum Albumin in Wistar Rats and Cynomolgus Monkeys: Implications for Dosage Regimens in the Therapy of HIV Infection

Drug Delivery
P J SwartD K Meijer

Abstract

Succinylation of serum albumin produces a negatively charged protein with a potent anti-HIV-1/2 and anti-SIVmac activity. The in vitro IC50 values of Suc-HSA against the respective primate lentiviruses are in the low nanomolar concentration range. Succinylated homologous serum albumin was given intravenously at four different doses, ranging from 0.1 to 10 mg/kg to Wistar rats and Cynomolgus monkeys. Plasma samples were assayed for their drug content using iodinated proteins. The pharmacokinetics parameters were calculated by a single compartment model, taking into account a potential saturable elimination process. In rats as well as in monkeys succinylated serum albumin clearly showed dose-dependent kinetics. The rate of Suc-SSA elimination from the bloodstream in macaques could be described by a Vmax of 11.7 ± 0.2 µg/min kg-(1) and a K. of 0.40 ± 0.06 µg/mL (5.5 nM). The elimination of Suc-RSA in rats was characterized by a 10-fold higher V. of 112 ± 29 µg/min kg(-1) and a much higher K. of 25 ± 9 µg/mL (340 nM). The volume of distribution was about the plasma volume for both species. In rats, no significant differences were found between the kinetic parameters of Suc-RSA, Suc-HSA, or Suc-SSA. Histochemical staining of tissue ...Continue Reading

References

Feb 1, 1992·AIDS Research and Human Retroviruses·E De Clercq
Feb 1, 1987·Journal of Pharmacokinetics and Biopharmaceutics·L B Sheiner, S L Beal
Jul 27, 1966·Biochimica Et Biophysica Acta·A Jobbágy, K Király
Jan 20, 1994·Biochemical Pharmacology·E De Clercq
Feb 1, 1994·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·A Erice, H H Balfour
Jun 1, 1995·AIDS Research and Human Retroviruses·L M GordonP W Mobley
May 1, 1994·Research in Virology·B HurtrelL Montagnier
Apr 15, 1996·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·M E KuipersD K Meijer

❮ Previous
Next ❯

Citations

May 20, 1997·AIDS Research and Human Retroviruses·P J SwartD K Meijer
Jan 11, 2000·Journal of Peptide Science : an Official Publication of the European Peptide Society·P J SwartD K Meijer
Aug 8, 2001·Journal of Pharmacological and Toxicological Methods·P OlingaG M Groothuis

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.